WO2025217554A1 - Systems and methods for detecting specific subspecies of autoantibodies and methods of use thereof - Google Patents

Abstract

A system and method for the detection of specific subclasses and isotypes of autoantibodies in saliva is described. In particular, the system is suitable for detecting distinct isotypes and subtypes of an autoantibody in a subject, wherein the level of the specific isotypes and subtypes of autoantibody is indicative of the presence or increased risk of development of an autoimmune disease or disorder.

Description

Attorney Docket No.206030-0295-00WO SYSTEMS AND METHODS FOR DETECTING SPECIFIC SUBSPECIES OF AUTOANTIBODIES AND METHODS OF USE THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63/633,023, filed April 11, 2024 which is hereby incorporated by reference herein in its entirety. STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT This invention was made with government support under DE030990 awarded by the National Institutes of Health. The government has certain rights in the invention. BACKGROUND OF THE INVENTION Sjögren’s disease (SD, also called Sjögren’s syndrome) is a systemic autoimmune disease characterized by the presence of lymphocytic infiltration of the exocrine glands and circulating anti-SSA/Ro and anti-SSB/La autoantibodies (Fox et al., 2002, Scand J Rheumatol Suppl;116:3-13; Brito-Zerón et al., 2016, Nat Rev Dis Primers, 2:16047; Mariette et al., 2018, N Engl J Med, 378:931-9). Exocrine glands, especially the salivary and lacrimal glands, are affected by the disease leading to salivary and lacrimal gland dysfunction with oral and ocular dryness. The mechanism underlying the development of SD is mainly believed to include a gradual inflammation of the glandular tissue induced by abnormal T- and B-cell responses to the autoantigens SSA and SSB (Brito-Zerón et al., 2016, Nat Rev Dis Primers, 2:16047). However, previous findings also indicate that the epithelial cells of the exocrine glands are not merely target of infiltrating immune cells, but they are actively involved in the autoimmune response (Manoussakis et al., 2010, J Autoimmun, 35:219-244, Alunno et al., 2015, Mediators Inflamm, 2437235). It has been shown that the salivary gland epithelial cells express human leukocyte antigen (HLA) class I molecules, adhesion molecules, tumor necrosis factor (TNF) receptor superfamily member 5 (i.e., CD40) and 6 (i.e., FAS receptor) and the FAS ligand, proinflammatory cytokines and chemokines that in various ways are involved in recruitment, homing, activation, differentiation, proliferation and organization of immune cells (Manoussakis et al., 2010, J Autoimmun, 35:219-244, Tzioufas et al., 2012, J Autoimmun, 39: 4-8). Cytokines produced by the infiltrating lymphocytes further contribute to upregulation of the molecules on the salivary gland epithelial cells. Salivary gland epithelial cells have also been shown to activate and mediate differentiation of CD4+T cells resulting in survival of B-cells (Manoussakis et al., 2010, J Autoimmun, 35:219-244, Tzioufas et al., 2012, J Autoimmun, 39: 4-8; Youino et al., 2012, Curr Pharm Biotechnol, 13:2071-7). Detection of anti-SSA/Ro and -SSB/La autoantibodies in serum and/or focal lymphocytic sialadenitis in labial salivary gland tissue is essential for the clinical diagnosis of SS (Vitali et al., 2002, Ann Rheum Dis, 61:554-88; Shiboski et al., 2017, Arthritis Rheumatol, 69:35-45; Shiboski et al., 2012, Arthritis Care Res (Hoboken), 64(4):475-87-10). The prevalence of serum anti-SSA/Ro and anti-SSB/La is reported to be 50-70% and 25- 40%, respectively (Fayyaz et al., 2016, Rheum Dis Clin North Am, 42:419-34). Moreover, patients with anti-SSA/Ro autoantibodies usually also have a more severe clinical manifestation than those who are seronegative. Analytical detection platforms that can effectively and quantitatively detect anti-SSA/Ro in saliva have now been reported. However, the presence of anti-SSA/Ro antibodies in saliva are consistent with multiple diseases and is therefore insufficient to distinguish SD from other conditions. There remains a need in the art for non-invasive systems and methods for diagnosing Sjögren’s disease and for distinguishing between primary Sjögren’s disease and SICCA syndrome. The present invention satisfies this need. SUMMARY OF THE INVENTION In one embodiment, the invention relates to a system comprising a device for detecting the presence or relative level of at least one subclass of at least one autoantibody in a subject, comprising: an array of units on a substrate, each unit comprising an electrode chip including a working electrode, a counter electrode, and a reference electrode; wherein the working electrode of at least one unit is coated with a conducting polymer embedded or functionalized with at least one capture antigen, wherein at least one capture antigen is a target antigen of an autoantibody, and at least one secondary binding molecule, wherein the secondary binding molecule binds to a specific isotype of autoantibody or subclass of autoantibody. In one embodiment, the secondary binding molecule is specific for the monomeric subclass of the autoantibody. In one embodiment, the target antigen is the 52 kDa SSA subunit (Ro-52) or a fragment thereof. In one embodiment, target antigen is the 60 kDa SSA subunit (Ro-60) or a fragment thereof. In one embodiment, the secondary binding molecule is specific for the IgM, IgD, IgG, IgE, IgA, IgA1, or IgA2 isotype of the autoantibody. In one embodiment, the secondary binding molecule is erythrina cristagalli lectin that specifically detects only monomeric IgA1. In one embodiment, the secondary binding molecule is specific for the monomeric or polymeric subclass of an anti-SSA/Ro autoantibody. In one embodiment, the secondary binding molecule is specific for the monomeric or polymeric subclass of an IgA1 anti-SSA/Ro autoantibody. In one embodiment, the invention relates to a method of detecting at least one specific subclass or isotype of an autoantibody in a subject comprising: obtaining a saliva sample from the subject; adding a first portion of the sample mixture to an electrode chip on a device comprising an array of units on a substrate, each unit comprising an electrode chip including a working electrode, a counter electrode, and a reference electrode; wherein the working electrode of at least one unit is coated with a conducting polymer embedded or functionalized with at least one capture antigen, wherein at least one capture antigen is a target antigen of an autoantibody; contacting the sample with a secondary binding molecule, wherein the secondary binding molecule binds to the specific isotype of autoantibody or subclass of autoantibody, or a combination thereof, and further wherein the secondary binding molecule is linked to a detectable moiety for generating a current; and measuring the current in the electrode chip, wherein a change in current is correlated to the presence of the specific subclass of the autoantibody in the sample. In one embodiment, the secondary binding molecule is specific for the monomeric subclass of the autoantibody. In one embodiment, the secondary binding molecule is specific for the IgM, IgD, IgG, IgE, IgA, IgA1, or IgA2 isotype of the autoantibody. In one embodiment, the secondary binding molecule is erythrina cristagalli lectin that specifically detects only monomeric IgA1. In one embodiment, the target antigen is the 52 kDa SSA subunit (Ro-52) or a fragment thereof. In one embodiment, the target antigen is the 60 kDa SSA subunit (Ro-60) or a fragment thereof. In one embodiment, the secondary binding molecule is specific for the monomeric subclass of an anti-SSA/Ro autoantibody. In one embodiment, the secondary binding molecule is specific for the monomeric subclass of an IgA1 anti-SSA/Ro autoantibody. In one embodiment, the invention relates to a method of diagnosing a disease associated with at least one specific subclass or isotype of an autoantibody in a subject comprising: obtaining a saliva sample from the subject; adding a first portion of the sample mixture to an electrode chip on a device comprising an array of units on a substrate, each unit comprising an electrode chip including a working electrode, a counter electrode, and a reference electrode; wherein the working electrode of at least one unit is coated with a conducting polymer embedded or functionalized with at least one capture antigen, wherein at least one capture antigen is a target antigen of an autoantibody; contacting the sample with a secondary binding molecule, wherein the secondary binding molecule binds to the specific isotype of autoantibody or subclass of autoantibody, or a combination thereof, and further wherein the secondary binding molecule is linked to a detectable moiety for generating a current; and measuring the current in the electrode chip, wherein a change in current is correlated to the presence of the specific subclass of the autoantibody in the sample. In one embodiment, the secondary binding molecule is specific for the monomeric subclass of the autoantibody. In one embodiment, the binding molecule is specific for the IgM, IgD, IgG, IgE, IgA, IgA1, or IgA2 isotype of the autoantibody. In one embodiment, the secondary binding molecule is molecule is erythrina cristagalli lectin that specifically detects only monomeric IgA1. In one embodiment, the target antigen is the 52 kDa SSA subunit (Ro-52) or a fragment thereof. In one embodiment, the target antigen is the 60 kDa SSA subunit (Ro-60) or a fragment thereof. In one embodiment, the secondary binding molecule is specific for the monomeric subclass of an anti-SSA/Ro autoantibody. In one embodiment, the secondary binding molecule is specific for the monomeric subclass of an IgA1 anti-SSA/Ro autoantibody. In one embodiment, the invention relates to a method of differentially diagnosing a subject as having or being at increased risk of primary Sjögren’s disease (pSD) or SICCA syndrome disease, the method comprising: obtaining a saliva sample from a subject identified as being at risk of SICCA or pSD; detecting the total IgA1 anti-SSA/Ro autoantibody in the sample; calculating the level or relative amount of at least one of the monomeric or polymeric subclass of the IgA1 type anti-SSA/Ro autoantibody in the sample from the difference in the level of the measured monomeric or polymeric subclass of the IgA1 type anti-SSA/Ro autoantibody in the sample and the detected total IgA1 type anti-SSA/Ro autoantibody in the sample; comparing the level or amount of at least one of the monomeric or polymeric subclass of the IgA1 anti-SSA/Ro autoantibody in the sample to a comparator control; and diagnosing the subject as having or being at risk of SICCA when an increased level of the monomeric IgA1 anti-SSA/Ro autoantibody is identified or diagnosing the subject as having or being at risk of pSD when an increased level of the polymeric IgA1 anti- SSA/Ro autoantibody is identified as compared to the comparator control. In one embodiment, the method further comprises: obtaining a saliva sample from a subject identified as being at risk of SICCA or pSD; adding a first portion of the sample mixture to an electrode chip on a device comprising an array of units on a substrate, each unit comprising an electrode chip including a working electrode, a counter electrode, and a reference electrode; wherein the working electrode of at least one unit is coated with a conducting polymer embedded or functionalized with at least one capture antigen, wherein at least one capture antigen comprises the 52 kDa SSA subunit (Ro52); contacting the sample with a secondary binding molecule, wherein the secondary binding molecule is specific for the monomeric or polymeric subclass of an IgA1 anti-SSA/Ro autoantibody, and further wherein the secondary binding molecule is linked to a detectable moiety for generating a current; and measuring the current in the electrode chip, wherein a change in current is correlated to the level or amount of the monomeric or polymeric subclass of the IgA1 anti- SSA/Ro autoantibody in the sample. In one embodiment, the comparator control is at least one selected from the group consisting of: an established cut-point, a positive control, a negative control, a historical control, a historical norm, a control subject, and the level of a reference molecule in the biological sample. In one embodiment, the method further comprises administering a therapeutic treatment for SICCA or pSD to the subject. BRIEF DESCRIPTION OF THE DRAWINGS The following detailed description of preferred embodiments of the invention will be better understood when read in conjunction with the appended drawings. For the purpose of illustrating the invention, there are shown in the drawings embodiments which are presently preferred. It should be understood, however, that the invention is not limited to the precise arrangements and instrumentalities of the embodiments shown in the drawings. Figure 1 depicts a schema of the EFIRM saliva anti-SSA/Ro-52 immuno- assay. Figure 2 depicts the performance of salivary isotypes to SSA/Ro-52 autoantibody to discriminate pSD, non-pSD SICCA, and healthy control subjects, which was determined by unpaired t-test. Statistical significance was considered achieved if the P-value was <0.05. Figure 3 depicts the performance of salivary isotypes to SSA/Ro-52 autoantibody to discriminate pSD, non-pSD SICCA, and healthy control subjects, which was determined by area under the ROC curves (AUC) with 95% confidence interval (CI). Figure 4 depicts a classification and Regression Tree model that discriminates healthy, pSD, and SICCA groups using six potential predicators (IgG, IgA, IgA1, IgA2, monomeric IgA1, and polymeric IgA1). The overall accuracy is 78.2% and specificity is 80.9% for neither pSD nor SICCA. Figure 5 depicts a two variable scatter plot of monomeric IgA1 and IgA1 (- nAmp) with color-coded points by group. The CART model selected potential cut-point at 339 IgA1 and 191 monomeric IgA1 which split the data into three distinct clusters. The classification accuracy of group status across these clusters was 80% indicating that there is an association between these markers and group. Figure 6 depicts the Z score for pIgA1, and mIgA1 for pSD and SICCA, where Z scores were computed by obtaining the overall mean for each marker (mIgA1 and pIgA1) and dividing by their respective standard deviations. DETAILED DESCRIPTION The present invention relates to methods of differentially diagnosing a subject as having or being at increased risk of a disease or disorder by, and assay systems and methods for, detecting the isotype and subclass of autoantibodies in a saliva sample of a subject in need thereof. In one embodiment, the invention provides an EFIRM assay system in which an antigen target for an autoantibody is incorporated as a capture antigen. In one embodiment, system further comprises a secondary binding molecule (e.g. a secondary antibody or lectin) that is specific for identifying the isotype or subclass of an autoantibody. In one embodiment, the antigen target bound by an anti-SSA/Ro autoantibody. In some embodiments, the assay system of the invention is used to diagnose a subject as having an autoimmune disease or disorder associated with the presence, absence or level of a specific isotype or subclass of an autoantibody. In some embodiments, the assay system of the invention is used to differentially diagnose a subject as having an autoimmune disease or disorder associated with the presence, absence or level of a specific isotype or subclass of an autoantibody. An exemplary autoimmune disease or disorder associated with the presence, absence or level of a specific isotype or subclass of an autoantibody is Sjögren's disease (SD). In one embodiment, an increased level of polymeric (pIgA1) autoantibody pIgA1 against SSA/Ro-52 or Ro-60 associated with primary Sjögren's disease (pSD). In one embodiment, an increased level of monomeric (mIgA1) autoantibody mIgA1 against SSA/Ro-52 or Ro-60 associated with SICCA syndrome. In one embodiment, the invention relates to methods of using the assay systems of the present invention to diagnose the presence or an increased risk of development of primary Sjögren’s disease. In one embodiment, the invention relates to methods of treating a subject identified as having or being at increased risk of developing primary Sjögren’s disease. In one embodiment, the invention relates to methods of using the assay systems of the present invention to diagnose the presence or an increased risk of development of SICCA syndrome. In one embodiment, the invention relates to methods of treating a subject identified as having or being at increased risk of developing SICCA syndrome. In one embodiment, the invention relates to methods of using the assay systems of the present invention to differentially diagnose the presence or an increased risk of development of primary Sjögren’s disease or SICCA syndrome. In one embodiment, the invention relates to methods of treating a subject identified as having or being at increased risk of developing primary Sjögren’s disease or SICCA syndrome. In one embodiment, the invention relates to a method of diagnosing a subject as having an autoimmune disease or disorder associated with the presence, absence or level of a specific isotype or subclass of an autoantibody. In some embodiments, the method of the invention is used to differentially diagnose a subject as having an autoimmune disease or disorder associated with the presence, absence or level of a specific isotype or subclass of an autoantibody. An exemplary autoimmune disease or disorder associated with the presence, absence or level of a specific isotype or subclass of an autoantibody is Sjögren’s disease (SD). In one embodiment, an increased level of polymeric (pIgA1) autoantibody pIgA1 against SSA/Ro-52 or Ro-60 associated with primary Sjögren's disease (pSD). In one embodiment, an increased level of monomeric (mIgA1) autoantibody mIgA1 against SSA/Ro-52 or Ro-60 associated with SICCA syndrome. Definitions Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described. As used herein, each of the following terms has the meaning associated with it in this section. The articles “a” and “an” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element. “About” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20%, ±10%, ±5%, ±1%, and ±0.1% from the specified value, as such variations are appropriate. The term “abnormal” when used in the context of organisms, tissues, cells or components thereof, refers to those organisms, tissues, cells or components thereof that differ in at least one observable or detectable characteristic (e.g., age, treatment, time of day, etc.) from those organisms, tissues, cells or components thereof that display the “normal” (expected) respective characteristic. Characteristics which are normal or expected for one cell or tissue type, might be abnormal for a different cell or tissue type. As used herein the terms “alteration,” “defect,” “variation,” or “mutation,” refers to a mutation in a gene in a cell that affects the function, activity, expression (transcription or translation) or conformation of the polypeptide that it encodes. Mutations encompassed by the present invention can be any mutation of a gene in a cell that results in the enhancement or disruption of the function, activity, expression or conformation of the encoded polypeptide, including the complete absence of expression of the encoded protein and can include, for example, missense and nonsense mutations, insertions, deletions, frameshifts and premature terminations. Without being so limited, mutations encompassed by the present invention may alter splicing the mRNA (splice site mutation) or cause a shift in the reading frame (frameshift). The term “amplification” refers to the operation by which the number of copies of a target nucleotide sequence present in a sample is multiplied. The term “antibody,” as used herein, refers to an immunoglobulin molecule which specifically binds with an antigen. Antibodies can be intact immunoglobulins derived from natural sources or from recombinant sources and can be immunoreactive portions of intact immunoglobulins. Antibodies are typically tetramers of immunoglobulin molecules. The antibodies in the present invention may exist in a variety of forms including, for example, polyclonal antibodies, monoclonal antibodies, Fv, Fab and F(ab)2, as well as single chain antibodies and humanized antibodies (Harlow et al., 1999, In: Using Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, NY; Harlow et al., 1989, In: Antibodies: A Laboratory Manual, Cold Spring Harbor, New York; Houston et al., 1988, Proc. Natl. Acad. Sci. USA 85:5879-5883; Bird et al., 1988, Science 242:423-426). An “antibody heavy chain,” as used herein, refers to the larger of the two types of polypeptide chains present in all antibody molecules in their naturally occurring conformations. An “antibody light chain,” as used herein, refers to the smaller of the two types of polypeptide chains present in all antibody molecules in their naturally occurring conformations. and light chains refer to the two major antibody light chain isotypes. The term “isotype” as used herein refers to the class of antibody as determined by the heavy- chain constant region (IgM, IgD, IgG, IgE, IgA). The term “subclass” herein refers to the form of the antibody, i.e. monomeric or polymeric (dimeric, trimeric, etc.). In serum, IgA is mainly present as a monomeric IgA that has a molecular weight of approximately 170,000, and IgA1 is a main component. A dimeric IgA is a dimeric IgA that is produced by plasma cells present in the mucosal lamina propria, and represents a molecule in which a heavy chain, a light chain and a J chain are present at a ratio of 4:4:1. In the dimeric IgA, IgA2 accounts for approximately half. Conventionally, dimeric or higher IgA recognized by a polymeric Ig receptor is often generally referred to as a polymeric IgA. That is, as a complex in which a heavy chain, a light chain and a J chain are present at a composition ratio of 4:4:1, a dimeric IgA in which two IgA molecules are associated via an antibody J-chain protein (a joining chain) is a main ingredient, and the term "polymeric IgA" is used both when it includes a secretory component protein (SC protein) and when it does not include an SC protein. That is, cases in which a polymeric IgA (a complex in which a heavy chain, a light chain and a J chain are present at a composition ratio of 4:4:1) secreted by plasma cells is referred to as a "polymeric IgA," cases in which a S-IgA (a complex in which a heavy chain, a light chain, a J chain and SC are present at a composition ratio of 4:4:1:1) secreted by mucosal epithelial cells is referred to as a "polymeric IgA," and cases in which it could refer to either are occasionally found, and thus these cases are not strictly distinguished. A component having a higher molecular weight than the dimeric IgA is often referred to as a polymeric IgA since the component is expected to be dimeric or higher. By the term “synthetic antibody” as used herein, is meant an antibody which is generated using recombinant DNA technology, such as, for example, an antibody expressed by a bacteriophage as described herein. The term should also be construed to mean an antibody which has been generated by the synthesis of a DNA molecule encoding the antibody and which DNA molecule expresses an antibody protein, or an amino acid sequence specifying the antibody, wherein the DNA or amino acid sequence has been obtained using synthetic DNA or amino acid sequence technology which is available and well known in the art. By the term “specifically binds,” as used herein with respect to an antibody, is meant an antibody which recognizes a specific antigen, but does not substantially recognize or bind other molecules in a sample. For example, an antibody that specifically binds to an antigen from one species may also bind to that antigen from one or more species. But such cross-species reactivity does not itself alter the classification of an antibody as specific. In another example, an antibody that specifically binds to an antigen may also bind to different allelic forms of the antigen. However, such cross reactivity does not itself alter the classification of an antibody as specific. In some instances, the terms “specific binding” or “specifically binding,” can be used in reference to the interaction of an antibody, a protein, or a peptide with a second chemical species, to mean that the interaction is dependent upon the presence of a particular structure (e.g., an antigenic determinant or epitope) on the chemical species; for example, an antibody recognizes and binds to a specific protein structure rather than to proteins generally. If an antibody is specific for epitope “A”, the presence of a molecule containing epitope A (or free, unlabeled A), in a reaction containing labeled “A” and the antibody, will reduce the amount of labeled A bound to the antibody. As used herein, the term “marker” or “biomarker” is meant to include a parameter which is useful according to this invention for determining the presence and/or severity of a disease or disorder. The level of a marker or biomarker “significantly” differs from the level of the marker or biomarker in a reference sample if the level of the marker in a sample from the patient differs from the level in a sample from the reference subject by an amount greater than the standard error of the assay employed to assess the marker, and preferably at least 10%, and more preferably 25%, 50%, 75%, or 100%. The term “control or reference standard” describes a material comprising none, or a normal, low, or high level of one of more of the marker (or biomarker) expression products of one or more the markers (or biomarkers) of the invention, such that the control or reference standard may serve as a comparator against which a sample can be compared. By the phrase “determining the level of marker (or biomarker) expression” is meant an assessment of the degree of expression of a marker in a sample at the nucleic acid or protein level, using technology available to the skilled artisan to detect a sufficient portion of any marker expression product. “Differentially increased expression” or “up regulation” refers to biomarker product levels which are at least 10% or more, for example, 20%, 30%, 40%, or 50%, 60%, 70%, 80%, 90% higher or more, and/or 1.1 fold, 1.2 fold, 1.4 fold, 1.6 fold, 1.8 fold, 2.0 fold higher or more, and any and all whole or partial increments therebetween than a control. “Differentially decreased expression” or “down regulation” refers to biomarker product levels which are at least 10% or more, for example, 20%, 30%, 40%, or 50%, 60%, 70%, 80%, 90% lower or less, and/or 2.0 fold, 1.8 fold, 1.6 fold, 1.4 fold, 1.2 fold, 1.1 fold or less lower, and any and all whole or partial increments therebetween than a control. A “disease” is a state of health of an animal wherein the animal cannot maintain homeostasis, and wherein if the disease is not ameliorated then the animal’s health continues to deteriorate. As used herein, an “instructional material” includes a publication, a recording, a diagram, or any other medium of expression which can be used to communicate the usefulness of a component of the invention in a kit for detecting biomarkers disclosed herein. The instructional material of the kit of the invention can, for example, be affixed to a container which contains the component of the invention or be shipped together with a container which contains the component. Alternatively, the instructional material can be shipped separately from the container with the intention that the instructional material and the component be used cooperatively by the recipient. The term “label” when used herein refers to a detectable compound or composition that is conjugated directly or indirectly to a probe to generate a “labeled” probe. The label may be detectable by itself (e.g., radioisotope labels or fluorescent labels) or, in the case of an enzymatic label, may catalyze chemical alteration of a substrate compound or composition that is detectable (e.g., avidin-biotin). In some instances, primers can be labeled to detect a PCR product. The “level” of one or more biomarkers means the absolute or relative amount or concentration of the biomarker in the sample. The term “marker (or biomarker) expression” as used herein, encompasses the transcription, translation, post-translation modification, and phenotypic manifestation of a gene, including all aspects of the transformation of information encoded in a gene into RNA or protein. By way of non-limiting example, marker expression includes transcription into messenger RNA (mRNA) and translation into protein, as well as transcription into types of RNA such as transfer RNA (tRNA) and ribosomal RNA (rRNA) that are not translated into protein. “Measuring” or “measurement,” or alternatively “detecting” or “detection,” means assessing the presence, absence, quantity or amount (which can be an effective amount) of either a given substance within a clinical or subject-derived sample, including the derivation of qualitative or quantitative concentration levels of such substances, or otherwise evaluating the values or categorization of a subject’s clinical parameters. The terms “patient,” “subject,” “individual,” and the like are used interchangeably herein, and refer to any animal, or cells thereof whether in vitro or in situ, amenable to the methods described herein. In certain non-limiting embodiments, the patient, subject or individual is a human. As used herein, the term “providing a prognosis” refers to providing a prediction of the probable course and outcome of a disease or disorder, including prediction of severity, duration, chances of recovery, etc. The methods can also be used to devise a suitable therapeutic plan. A “reference level” of a biomarker means a level of the biomarker that is indicative of a particular disease state, phenotype, or lack thereof, as well as combinations of disease states, phenotypes, or lack thereof. A “positive” reference level of a biomarker means a level that is indicative of a particular disease state or phenotype. A “negative” reference level of a biomarker means a level that is indicative of a lack of a particular disease state or phenotype. “Sample” or “biological sample” as used herein means a biological material isolated from an individual. The biological sample may contain any biological material suitable for detecting the desired biomarkers and may comprise cellular and/or non-cellular material obtained from the individual. “Standard control value” as used herein refers to a predetermined amount of a particular protein or nucleic acid that is detectable in a sample, such as a saliva sample, either in whole saliva or in saliva supernatant. The standard control value is suitable for the use of a method of the present invention, in order for comparing the amount of a protein or nucleic acid of interest that is present in a saliva sample. An established sample serving as a standard control provides an average amount of the protein or nucleic acid of interest in the saliva that is typical for an average, healthy person of reasonably matched background, e.g., gender, age, ethnicity, and medical history. A standard control value may vary depending on the protein or nucleic acid of interest and the nature of the sample (e.g., whole saliva or supernatant). Throughout this disclosure, various aspects of the invention can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, 6 and any whole and partial increments therebetween. This applies regardless of the breadth of the range. Description The present invention relates to a method of differentially diagnosing disease based upon detection of the presence or relative level of specific autobody subclasses in saliva. In some aspects, the present invention relates to an assay to differentially diagnose disease based upon detection of the presence or relative level of specific autobody subclasses. In some embodiments, the assay of the invention includes methods for autoantibody detection employing an electrical field induced release and measurement (EFIRM) system. In some aspects the presence or relative level of monomeric and polymeric forms of autoantibodies are detected in a saliva sample of a subject using the developed assay. In some aspects autoantibodies are detected from saliva of subjects having or having an increased risk of a disease or disorder. In some embodiments, the subject has or is at risk of having SD. In some embodiments, the subject has or is at risk of having SICCA. While the present invention is described generally for the detection of Anti- SSA/Ro autoantibody subclass in a saliva sample, it should be appreciated that the subclass of any autoantibody that is present in a saliva sample can be detected using the methods of the invention. Non-limiting examples of such detectible autoantibodies include those associated with autoimmune diseases and disorders. It should be appreciated that any number of autoantibodies can be detected using the assay platform, including, without limitation, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more than 10 autoantibodies. It should be appreciated that distinct isotypes, subclasses, or a combination thereof, of autoantibodies can be detected using the assay platform. It should be appreciated that the presence or relative level of different subclasses of autoantibodies can be detected using the assay platform. The noninvasive detection of the presence or relative level of different autoantibodies in a subject via the present invention enables clinicians to identify the presence or risk of an autoimmune disease or disorder in a fast, economical and non-invasive manner. EFIRM System As contemplated herein, the present invention includes a method of detecting the presence or relative level of different autoantibodies using a multiplexing electrochemical sensor. In one embodiment, the device utilizes a small sample volume with high accuracy. In addition, multiple autoantibodies can be measured simultaneously on the device with single sample loading. The device may significantly reduce the cost to the health care system, by decreasing the burden of patients returning to clinics and laboratories. In one embodiment, the electrochemical sensor is an array of electrode chips (GeneFluidics, USA). In some embodiments, each unit of the array has a working electrode, a counter electrode, and a reference electrode. The three electrodes may be constructed of bare gold or other conductive material before the reaction, such that one or more antigens may be immobilized on the working electrode. Electrochemical current can be measured between the working electrode and counter electrode under the potential between the working electrode and the reference electrode. The potential profile can be a constant value, a linear sweep, or a cyclic square wave, for example. An array of plastic wells may be used to separate each three-electrode set, which helps avoid cross contamination between different sensors. A conducting polymer may also be deposited on the working electrodes as a supporting film, and in some embodiments, as a surface to functionalize the working electrode. As contemplated herein, any conductive polymer may be used, such as polypyrroles, polanilines, polyacetylenes, polyphenylenevinylenes, polythiophenes and the like. In one embodiment, a cyclic square wave electric field (csw E-field) is generated across the electrode within the sample well. In certain embodiments, the square wave electric field is generated to aid in polymerization of one or more capture antigens to the polymer of the sensor. In certain embodiments, the square wave electric field is generated to aid in the hybridization of the capture antigen with the autoantibody to be detected and/or detector probe (e.g., secondary binding molecule). The positive potential in the csw E-field helps the antigenic molecules accumulate onto the working electrode, while the negative potential removes the weak nonspecific binding, to generate enhanced specificity. Further, the flapping between positive and negative potential across the cyclic square wave also provides superior mixing during incubation, without disruption of the desired specific binding, which accelerates the binding process and results in a faster test or assay time. In one embodiment, a square wave cycle may consist of a longer low voltage period and a shorter high voltage period, to enhance binding partner hybridization within the sample. While there is no limitation to the actual time periods selected, examples include 0.15 to 60 second low voltage periods and 0.1 to 60 second high voltage periods. In a preferred embodiment, each square-wave cycle consists of 1 s at low voltage and 1 s at high voltage. For hybridization, the low voltage may be around 200 mV and the high voltage may be around +500 mV. In some embodiments, the total number of square wave cycles may be between 2-50. In one embodiment, 5 cyclic square-waves are applied for each surface reaction. With the csw E-field, both the polymerization and hybridization are finished on the same chip within minutes. In some embodiments, the total detection time from sample loading is less than 30 minutes. In other embodiments, the total detection time from sample loading is less than 20 minutes. In other embodiments, the total detection time from sample loading is less than 10 minutes. In other embodiments, the total detection time from sample loading is less than 5 minutes. In other embodiments, the total detection time from sample loading is less than 2 minutes. In other embodiments, the total detection time from sample loading is less than 1 minute. In one embodiment, a multi-channel electrochemical reader (GeneFluidics) controls the electrical field applied onto the array sensors and reports the amperometric current simultaneously. In practice, solutions can be loaded onto the entire area of the three- electrode region including the working, counter, and reference electrodes, which are confined and separated by the array of plastic wells. After each step, the electrochemical sensors can be rinsed with ultrapure water or other washing solution and then dried, such as under pure N2. In some embodiments, the sensors are single use, disposable sensors. In another embodiment, the sensors are reusable. As contemplated herein, the assay platform may be organized as any type of affinity binding assay or immunoassay as would be understood by those skilled in the art. In one embodiment, the present invention is based on the affinity between a capture antigen comprising a target antigen of an autoantibody, an autoantibody of interest, and a secondary binding molecule (e.g. a secondary antibody or lectin) for recognition of a bound autoantibody, which functions as a detector probe. In another embodiment, the present invention includes a single platform for multiple autoantibody measurements, instead of a single autoantibody. In one embodiment, the secondary binding molecule recognizes specifically the monomeric or polymeric isotype of an autoantibody. In one embodiment, the present invention is efficient in that it is simple, rapid and robust. For example, only small sample volumes are needed (e.g., 10 l) and less than 10 minutes run time are needed. Multiple marker levels may be provided by the device. By providing statistical analysis the user may have an estimate of their risk, and by utilizing available networking systems, the results can be quickly transmitted for review by a clinician for further assessment. In one embodiment, an antigen for recognition by an autoantibody is coated onto the electrode and serves as a capture antigen. Exemplary autoantibody target antigens that can be used as capture antigens include, but are not limited to, ribonuceloproteins, histidine-tRNA ligase, snRNP core proteins, Type I topoisomerase, histones, nucleoporin 62, Sp100 nuclear antigen, nucleoporin 210kDa, ganglioside GQ1B, ganglioside G3D, ganglioside GM1, actin cyclic citrullinated peptide, thrombin, phospholipid, IgG, glutamate receptor, glutamate decarboxylase, voltage-gated potassium channel, neuronal nuclear proteins, thyroglobulin, TSH receptor, vinculin, muscle-specific kinase, voltage-gated calcium channel, nicotinic acetylcholine receptor, aquaporin-4, N-methyl-D-aspartate receptor, single or double stranded DNA, and collapsing response mediator protein 5. In one embodiment, the antigen is the 52 kDa SSA subunit or a fragment thereof. The capture antigen is coated onto the bare gold electrode by applying a cyclic square wave electric field. For example, for each cycle during the coating step, the electric field can be set to +350 mV for 1 s and +950 mV for 1 s. In total, coating of the electrode may proceed for 5 cycles, for a total of 10s, or however long is deemed necessary. Capture antigens used to functionalize the working electrode surface may be constructed according to any protocol known in the art for the generation of peptides. After antigen coating, the sensor chip can be rinsed and dried for subsequent sample measurement. Samples containing an autoantibody to be detected, such as a cell- culture medium, a blood sample or a saliva sample, can be mixed with a secondary binding molecule (e.g. a secondary antibody or lectin) and transferred onto the electrodes. Hybridization of the autoantibody to the capture antigen occurs during incubation for an appropriate amount of time and in appropriate conditions for the autoantibody to bind to the antigen. Following hybridization, any unbound antibodies can be removed by washing. Next, the antigen-bound antibodies are detected. In one embodiment, a secondary binding molecule (e.g. a secondary antibody or lectin) that binds to the autoantibody to be detected is used as a direct or indirect detector molecule. The detector molecules (e.g., secondary binding molecules) can be labeled, such as with fluorescein isothiocyanate, Alexa Fluor, HRP, Biotin, or any other label known in the art. In one embodiment, the secondary binding molecule is labeled with biotin and is then contacted with a streptavidin bound molecule for generating a detectable readout, allowing for indirect detection of the secondary binding molecule bound to the autoantibody:antigen complex. In one embodiment, the streptavidin bound molecule comprises poly-horseradish peroxidase. For example, in one embodiment horseradish peroxidase in casein-phosphate-buffered saline _{can be used, and the 3,3 ,5,5 -tetramethylbenzidine substrate for horseradish peroxidase can} be loaded, and the amperometric signal measured. In one embodiment, the detector probe comprises a secondary binding molecule (e.g. a secondary antibody or lectin) linked to a detectable label which induces a change in current of the sensor, thereby indicating the binding of the secondary binding molecule, and autoantibody, with the capture antigen. In certain embodiments, the detectable label itself may be sufficient to alter the current of the sensor. In certain embodiments, the detectable label induces the change in current when it comes into contact with an exogenous reactant. For example, the detectable label may react with the reactant to produce a local change sensed by the electrodes of the sensor to produce an amperometric signal. Therefore, in certain embodiments, the reactant is added to the sensor prior, during, or after the application of the sample to the sensor. In certain embodiments, the detectable label is directly conjugated to the detector probe. In another embodiment, the detectable label is bound to the detector probe via an intermediate tag or label of the probe. For example, in one embodiment, the detector probe comprises a tag, label, or epitope, which can be used to bind to an antibody or other binding compound harboring the detectable label described above. Examples of detectable labels and reactants to produce a local change in an electrochemical sensor are well known in the art. In one embodiment, the detectable label comprises HRP and the reactant is TMB, which react to generate an amperometric signal. In another embodiment, the detectable label comprises urease, while the reactant comprises urea. There is no limitation to the concentrations of such probes used, and may be optimized as needed by the user. Due to the sensitivity of the present invention, very small volumes may be used to perform the desired assays. For example, the biological sample size from the subject may be between 5-100 microliters. In one embodiment, the sample size need only be about 40 microliters. There is no limitation to the actual or final sample size to be tested. The present invention also relates to methods of detecting the presence or relative level of at least one autoantibody in a saliva sample of a subject. In one embodiment, the method specifically detects the presence or relative level of the monomeric and/or polymeric subclass of an autoantibody in a saliva sample of a subject. In one embodiment, the method may be performed as an immunoassay assay and includes the steps of obtaining a sample from the subject, applying the sample to an electrode chip coated with a conducting polymer previously embedded or functionalized with a capture antigen comprising a target antigen of an autoantibody to be detected, or a fragment thereof, contacting the sample with a secondary binding molecule (e.g. a secondary antibody or lectin) wherein the secondary binding molecule is linked to a detectable moiety for generating a current, and measuring the current in the electrode chip. The detectable moiety may be measured, or the magnitude of the current in the sample may be measured, to determine the presence or absence of at least one autoantibody in the sample. In certain embodiments, binding of the autoantibody marker to the electrode of the sensor results in an increase in current or negative current. For example, in one embodiment, binding results in a current in the range of about -10nA to about -1000nA. In one embodiment, the secondary binding molecule (e.g. a secondary antibody or lectin) that recognizes a specific isotype of an autoantibody. In one embodiment, the secondary binding molecule comprises a erythrina cristagalli lectin (ECL) that recognizes specifically the monomeric form of an autoantibody isotype (e.g., monomeric IgA1). In one embodiment, the abundance of the polymeric form of an autoantibody isotype is determined by subtracting the measurements from ECL that specifically binds the monomeric form of the autoantibody isotype from the measurements from a secondary binding molecule that binds all forms of the autoantibody isotype. Methods of Detecting Autoantibody Subclass In some embodiments, the present invention provides methods of detecting the presence or relative level of at least one subclass of an autoantibody in a biological sample of a subject. In one embodiment, the method specifically detects the presence or relative level of the monomeric and/or polymeric subclass of an autoantibody in a biological sample of a subject. In one embodiment, the method specifically detects the presence or relative level of mIgA1 in a biological sample of a subject. In one embodiment, the method may be performed as an immunoassay assay and includes the steps of obtaining a sample from the subject, applying the sample to a capture antigen comprising a target antigen of the autoantibody to be detected, or fragment thereof, and contacting the sample with a secondary binding molecule (e.g. a secondary antibody or lectin) wherein the secondary binding molecule detects a specific isotype and/or subclass of the autoantibody. In one embodiment, the abundance of one subclass of an autoantibody isotype is determined by subtracting the measurements from a secondary binding molecule (e.g. a secondary antibody or lectin) that specifically binds the other subclass of the autoantibody isotype from the measurements from a secondary binding molecule that binds all forms of the autoantibody isotype. In one embodiment, the method specifically detects the presence or relative level of mIgA1 in a biological sample of a subject by contacting a sample with a lectin ECL that specifically detects only mIgA1, contacting a sample with a secondary binding molecule (e.g. a secondary antibody or lectin) that detects total IgA1, and subtracting the level of the detected mIgA1 from the total IgA1 to obtain the relative level of pIgA1. In various embodiments, the level of one or more of markers of the invention in the biological sample of the subject is compared with the level of a corresponding biomarker in a comparator. Non-limiting examples of comparators include, but are not limited to, a negative control, a positive control, an expected normal background value of the subject, a historical normal background value of the subject, an expected normal background value of a population that the subject is a member of, or a historical normal background value of a population that the subject is a member of. In one embodiment, a biological sample from a subject is assessed for the level of one or more of an autoantibody or subclass of said autoantibody. In some embodiments, the level of one or more of an autoantibody or subclass of said autoantibody of the invention is determined to be increased when the level of one or more of an autoantibody or subclass of said autoantibody detected in a biological sample of a subject is increased when compared to with a comparator control. In one embodiment, the comparator control is a positive control, a negative control, a historical control, a historical norm, or the level of a reference molecule in the biological sample. In various embodiments, to determine whether the level of one or more of an autoantibody or subclass of said autoantibody of the invention is increased, the level of one or more of an autoantibody or subclass of said autoantibody, the total level of a specific subtype or subclass of the antibody (e.g., polymeric or monomeric subtype) in the sample is compared with the level of at least one comparator control, such as a positive control, a negative control, a historical control, a historical norm, or the level of another reference molecule in the biological sample. In some embodiments, the level of a specific subtype or subclass of an autoantibody (e.g., polymeric or monomeric subtype) in the sample is compared with the total amount of autoantibody present in the sample to determine the relative amount or percentage(s) of the specific subtype or subclass of an autoantibody (e.g., polymeric or monomeric subtype) are present in the sample. In some embodiments, the relative amount or percentage(s) of the specific subtype or subclass of autoantibody (e.g., polymeric or monomeric subtype) is compared with the level of at least one comparator control, such as a positive control, a negative control, a historical control, a historical norm, or the level of another reference molecule in the biological sample. Methods of Differential Diagnosis In one embodiment, the present invention provides methods for diagnosing, determining risk or treating a disease or disorder associated with the presence or relative level of at least one autoantibody in a subject. Accordingly, the present invention features methods for identifying subjects who are at risk of developing autoimmune diseases, including, but not limited to, rheumatoid arthritis/seronegative arthropathies, osteoarthritis, inflammatory bowel disease, systemic lupus erythematosis, iridoeyelitis/uveitistoptic neuritis, idiopathic pulmonary fibrosis, systemic vasculitis/Wegener's gramilornatosis, sarcoidosis, including, but not limited to, rheumatoid arthritis/seronegative arthropathies, osteoarthritis, inflammatory bowel disease, systemic lupus erythematosis, iridoeyelitis/uveitistoptic neuritis, idiopathic pulmonary fibrosis, systemic vasculitis/Wegener's gramilornatosis, sarcoidosis, myocarditis, postmyocardial infarction syndrome, postpericardiotomy syndrome, subacute bacterial endocarditis (SBE), anti-glomerular basement membrane nephritis, interstitial cystitis, lupus nephritis, autoimmune hepatitis, primary biliary cholangitis(PBC), primary sclerosing cholangitis, antisynthetase syndrome, alopecia areata, autoimmune angioedema, autoimmune progesterone dermatitis, autoimmune urticaria, bullous pemphigoid, cicatricial pemphigoid, dermatitis herpetiformis, discoid lupus erythematosus, epidermolysis bullosa acquisita, erythema nodosum, gestational pemphigoid, hidradenitis suppurativa, lichen planus, lichen sclerosus, linear IgA disease (LAD), morphea, pemphigus vulgaris, pityriasis lichenoides et varioliformis acuta, Mucha-Habermann disease, psoriasis, systemic scleroderma, vitiligo, Addison's disease, autoimmune polyendocrine syndrome (APS) type 1, autoimmune polyendocrine syndrome (APS) type 2, autoimmune polyendocrine syndrome (APS) type 3, autoimmune pancreatitis (AIP), diabetes mellitus type 1, autoimmune thyroiditis, Ord's thyroiditis, Graves' disease, autoimmune oophoritis, endometriosis, autoimmune orchitis, Sjogren's syndrome, autoimmune enteropathy, Coeliac disease, Crohn's disease, microscopic colitis, ulcerative colitis, antiphospholipid syndrome(APS, APLS), aplastic anemia, autoimmune hemolytic anemia, autoimmune lymphoproliferative syndrome, autoimmune neutropenia, autoimmune thrombocytopenic purpura, cold agglutinin disease, essential mixed cryoglobulinemia, Evans syndrome, pernicious anemia, pure red cell aplasia, thrombocytopenia, adiposis dolorosa, adult-onset Still's disease, ankylosing spondylitis, CREST syndrome, drug-induced lupus, enthesitis-related arthritis, eosinophilic fasciitis Felty syndrome, IgG4-related disease, juvenile arthritis, Lyme disease (chronic), mixed connective tissue disease (MCTD), palindromic rheumatism, Parry Romberg syndrome, Parsonage- Turner syndrome, psoriatic arthritis, reactive arthritis, relapsing polychondritis, retroperitoneal fibrosis, rheumatic fever, Schnitzler syndrome, undifferentiated connective tissue disease (UCTD), dermatomyositis, fibromyalgia, inclusion body myositis, myositis, myasthenia gravis, neuromyotonia, paraneoplastic cerebellar degeneration, polymyositis, acute disseminated encephalomyelitis (ADEM), acute motor axonal neuropathy, anti-N- methyl-D-aspartate (Anti-NMDA) receptor encephalitis, balo concentric sclerosis, Bickerstaff's encephalitis, chronic inflammatory demyelinating polyneuropathy, Guillain– Barré syndrome, Hashimoto's encephalopathy, idiopathic inflammatory demyelinating diseases, Lambert-Eaton myasthenic syndrome, multiple sclerosis, pattern II, Oshtoran Syndrome, pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS), progressive inflammatory neuropathy, restless leg syndrome, stiff person syndrome, sydenham chorea, transverse myelitis, autoimmune retinopathy, autoimmune uveitis, Cogan syndrome, Graves ophthalmopathy, intermediate uveitis, ligneous conjunctivitis, Mooren's ulcer, neuromyelitis optica, opsoclonus myoclonus syndrome, optic neuritis, scleritis, Susac's syndrome, sympathetic ophthalmia, Tolosa-Hunt syndrome, autoimmune inner ear disease(AIED), Ménière's disease, Behçet's disease, eosinophilic granulomatosis with polyangiitis (EGPA), giant cell arteritis, granulomatosis with polyangiitis (GPA), IgA vasculitis (IgAV), Kawasaki's disease, leukocytoclastic vasculitis, lupus vasculitis, rheumatoid vasculitis, microscopic polyangiitis (MPA), polyarteritis nodosa (PAN), polymyalgia rheumatic, urticarial vasculitis, vasculitis, and primary immune deficiency. In one embodiment, the disease or disorder is associated with the presence or an increased level of the monomeric form of an IgA Anti-SSA/Ro autoantibody. Exemplary diseases associated with the presence or an increased level of the monomeric form of an IgA1 Anti-SSA/Ro autoantibody include, but are not limited to, SICCA syndrome. In one embodiment, the disease or disorder is associated with the presence or an increased level of the polymeric form of an IgA Anti-SSA/Ro autoantibody. Exemplary diseases associated with the presence or an increased level of the polymeric form of an IgA1 Anti-SSA/Ro autoantibody include, but are not limited to, primary Sjogren’s disease. In one embodiment, a disease or disorder can be distinguished from another disease or disorder based on the abundance of the monomeric and/or polymeric form of the autoantibody. For example, in one embodiment, the relative abundance of the monomeric and polymeric subclasses of an IgA Anti-SSA/Ro autoantibody is used to differentially diagnose a subject as having SICCA syndrome or primary Sjogren’s disease. In a number of specific autoimmune diseases, such as Sjogren’s disease, autoantibodies appear before the disease clinical onset is presented. The methods of the invention are also useful for monitoring subjects undergoing treatments and therapies for an autoimmune disease or disorder associated with at least one autoantibody, and for selecting or modifying therapies and treatments that would be efficacious in subjects having an autoimmune disease or disorder, wherein selection and use of such treatments and therapies slow the progression of one or more autoimmune disease, or prevent their onset. The invention provides improved diagnosis and prognosis of an autoimmune disease or disorder associated with at least one autoantibody. The risk of developing an autoimmune disease or disorder associated with at least one autoantibody can be assessed by measuring one or more autoantibody as described herein, and comparing the measured values to reference or index values. Subjects identified as having an increased level of at least one specific subclass of an autoantibody can optionally be selected to receive treatment regimens, such as administration of prophylactic or therapeutic compounds or treatments to prevent, treat or delay the onset of an autoimmune disease or disorder associated with at least one autoantibody. Identifying a subject before they develop an autoimmune disease or disorder associated with at least one specific subclass of an autoantibody enables the selection and initiation of various therapeutic interventions or treatment regimens in order to delay, reduce or prevent the development or severity of the disease or disorder. In certain instances, monitoring the levels of at least one specific subclass of an autoantibody also allows for the course of treatment of the disease or disorder to be monitored. For example, a sample can be provided from a subject undergoing treatment regimens or therapeutic interventions (e.g., drug treatments, immunosuppressive therapy, etc.) for an autoimmune disease or disorder. Samples can be obtained from the subject at various time points before, during, or after treatment. Data concerning the presence or levels of the specific subclasses of autoantibodies of the present invention can also be combined or correlated with other data or test results, including but not limited to imaging data, medical history and any relevant family history. The present invention also provides methods for identifying agents for treating an autoimmune disease or disorder that are appropriate or otherwise customized for a specific subject. In this regard, a test sample from a subject, exposed to a therapeutic agent, drug, or other treatment regimen, can be taken and the level of one or more autoantibody can be determined. The level of one or more specific subclass of an autoantibody can be compared to in a sample derived from the subject before and after treatment, or can be compared across samples derived from one or more subjects who have shown improvements in risk factors as a result of such treatment or exposure. In some embodiments, these methods may utilize a biological sample (such as urine, saliva, blood, serum, amniotic fluid, or tears), for the detection of one or more autoantibody in the sample. In one embodiment, the sample is a saliva sample. Frequently the sample will be a “clinical sample” which is a sample derived from a patient. In various embodiments, the level of one or more of markers of the invention in the biological sample of the subject is compared with the level of a corresponding biomarker in a comparator. Non-limiting examples of comparators include, but are not limited to, a negative control, a positive control, an expected normal background value of the subject, a historical normal background value of the subject, an expected normal background value of a population that the subject is a member of, or a historical normal background value of a population that the subject is a member of. In some embodiments, the invention provides methods of diagnosing, monitoring the progression of, or treating an autoimmune disease or disorder associated with at least one specific subclass of an anti-SSA/Ro autoantibody in a subject by assessing the level of one or more of an anti-SSA/Ro autoantibody or at least one isotype or subclass of an anti-SSA/Ro autoantibody in a biological sample of the subject. In various embodiments, the subject is a human subject, and may be of any race, sex and age. Information obtained from the methods of the invention described herein can be used alone, or in combination with other information (e.g., disease status, disease history, vital signs, blood chemistry, etc.) from the subject or from the biological sample obtained from the subject. In some embodiments, the level of one or more autoantibody or subclass of an autoantibody is determined to be increased when the level of the autoantibody or subclass of the autoantibody detected in a biological sample of a subject is increased by at least 10%, by at least 20%, by at least 30%, by at least 40%, by at least 50%, by at least 60%, by at least 70%, by at least 80%, by at least 90%, or by at least 100%, when compared to with a comparator control. In one embodiment, a biological sample from a subject is assessed for the level of one or more of an anti-SSA/Ro autoantibody or subclass of said autoantibody. In some embodiments, the level of one or more of an anti-SSA/Ro autoantibody or subclass of said autoantibody of the invention is determined to be increased when the level of one or more of an anti-SSA/Ro autoantibody or subclass of said autoantibody detected in a biological sample of a subject is increased when compared to with a comparator control. In one embodiment, the comparator control is a positive control, a negative control, a historical control, a historical norm, or the level of a reference molecule in the biological sample. In various embodiments, to determine whether the level of one or more of an anti-SSA/Ro autoantibody or subclass of said autoantibody of the invention is increased, the level of one or more of an anti-SSA/Ro autoantibody or subclass of said autoantibody, the total level of a specific subtype or subclass of the antibody (e.g., polymeric or monomeric subtype) in the sample is compared with the level of at least one comparator control, such as a positive control, a negative control, a historical control, a historical norm, or the level of another reference molecule in the biological sample. In some embodiments, the level of a specific subtype or subclass of an anti-SSA/Ro autoantibody (e.g., polymeric or monomeric subtype) in the sample is compared with the total amount of anti-SSA/Ro autoantibody present in the sample to determine the relative amount or percentage(s) of the specific subtype or subclass of an anti-SSA/Ro autoantibody (e.g., polymeric or monomeric subtype) are present in the sample. In some embodiments, the relative amount or percentage(s) of the specific subtype or subclass of an anti-SSA/Ro autoantibody (e.g., polymeric or monomeric subtype) is compared with the level of at least one comparator control, such as a positive control, a negative control, a historical control, a historical norm, or the level of another reference molecule in the biological sample. In various embodiments of the assays of the invention, the level of the specific subtype or subclass of an anti-SSA/Ro autoantibody (e.g., polymeric or monomeric subtype) is determined to be elevated when the level of the specific subtype or subclass of an anti- SSA/Ro autoantibody (e.g., polymeric or monomeric subtype), or the percentage of the specific subtype or subclass of an anti-SSA/Ro autoantibody (e.g., polymeric or monomeric subtype) in the sample, is increased by at least 10%, by at least 20%, by at least 30%, by at least 40%, by at least 50%, by at least 60%, by at least 70%, by at least 80%, by at least 90%, by at least 100%, by at least 125%, by at least 150%, by at least 175%, by at least 200%, by at least 250%, by at least 300%, by at least 400%, by at least 500%, by at least 600%, by at least 700%, by at least 800%, by at least 900%, by at least 1000%, by at least 1500%, by at least 2000%, by at least 2500%, by at least 3000%, by at least 4000%, or by at least 5000%, when compared with a comparator control. In various embodiments of the assays of the invention, the level of the specific subtype or subclass of an anti-SSA/Ro autoantibody (e.g., polymeric or monomeric subtype) is determined to be elevated when the level of the specific subtype or subclass of an anti- SSA/Ro autoantibody (e.g., polymeric or monomeric subtype), or the percentage of the specific subtype or subclass of an anti-SSA/Ro autoantibody (e.g., polymeric or monomeric subtype) in the sample, is increased by at least 1.2 fold, at least 1.3 fold, at least 1.4 fold, at least 1.5 fold, at least 1.6 fold, at least 1.7 fold, at least 1.8 fold, at least 1.9 fold, at least 2.0 fold, at least 2.1 fold, at least 2.2 fold, at least 2.3 fold, at least 2.4 fold, at least 2.5 fold, at least 2.6 fold, at least 2.7 fold, at least 2.8 fold, at least 2.9 fold, at least 3.0 fold, at least 3.5 fold, at least 4.0 fold, at least 4.5 fold, at least 5.0 fold, at least 5.5 fold, at least 6 fold, at least 6.5 fold, at least 7 fold, at least 7.5 fold, at least 8 fold, at least 8.5 fold, at least 9 fold, at least 9.5 fold, at least 10 fold, at least 11 fold, at least 12 fold, at least 13 fold, at least 14 fold, at least 15 fold, at least 20 fold, at least 25 fold, at least 30 fold, at least 40 fold, at least 50 fold, at least 75 fold, at least 100 fold, at least 200 fold, at least 250 fold, at least 500 fold, or at least 1000 fold, when compared with a comparator control. In various embodiments of the assays of the invention, the level of the specific subtype or subclass of an anti-SSA/Ro autoantibody (e.g., polymeric or monomeric subtype) is determined to be decreased when the level of the specific subtype or subclass of an anti- SSA/Ro autoantibody (e.g., polymeric or monomeric subtype), or the percentage of the specific subtype or subclass of an anti-SSA/Ro autoantibody (e.g., polymeric or monomeric subtype) in the sample is decreased by at least 10%, by at least 20%, by at least 30%, by at least 40%, by at least 50%, by at least 60%, by at least 70%, by at least 80%, by at least 90%, by at least 100%, by at least 125%, by at least 150%, by at least 175%, by at least 200%, by at least 250%, by at least 300%, by at least 400%, by at least 500%, by at least 600%, by at least 700%, by at least 800%, by at least 900%, by at least 1000%, by at least 1500%, by at least 2000%, by at least 2500%, by at least 3000%, by at least 4000%, or by at least 5000%, when compared with a comparator control. In various embodiments of the assays of the invention, the level of the specific subtype or subclass of an anti-SSA/Ro autoantibody (e.g., polymeric or monomeric subtype) is determined to be decreased when the level of the specific subtype or subclass of an anti- SSA/Ro autoantibody (e.g., polymeric or monomeric subtype), or the percentage of the specific subtype or subclass of an anti-SSA/Ro autoantibody (e.g., polymeric or monomeric subtype) in the sample is decreased by at least 1.2 fold, at least 1.3 fold, at least 1.4 fold, at least 1.5 fold, at least 1.6 fold, at least 1.7 fold, at least 1.8 fold, at least 1.9 fold, at least 2.0 fold, at least 2.1 fold, at least 2.2 fold, at least 2.3 fold, at least 2.4 fold, at least 2.5 fold, at least 2.6 fold, at least 2.7 fold, at least 2.8 fold, at least 2.9 fold, at least 3.0 fold, at least 3.5 fold, at least 4.0 fold, at least 4.5 fold, at least 5.0 fold, at least 5.5 fold, at least 6 fold, at least 6.5 fold, at least 7 fold, at least 7.5 fold, at least 8 fold, at least 8.5 fold, at least 9 fold, at least 9.5 fold, at least 10 fold, at least 11 fold, at least 12 fold, at least 13 fold, at least 14 fold, at least 15 fold, at least 20 fold, at least 25 fold, at least 30 fold, at least 40 fold, at least 50 fold, at least 75 fold, at least 100 fold, at least 200 fold, at least 250 fold, at least 500 fold, or at least 1000 fold, when compared with a comparator control. Methods of Treatment The present invention also provides a method of treating or preventing an autoimmune disease or disorder, or reducing at least one symptom associated with an autoimmune disease or disorder in a subject. In one embodiment, the method comprises administering an effective amount of a therapeutic composition to, or performing a therapeutic procedure on, a subject identified by the methods of the invention as having or being at increased risk of developing an autoimmune disease or disorder through detection of an autoantibody in a biological sample of the subject. In one embodiment, the therapeutic composition comprises at least one therapeutic agent to treat the patient’s disease or disorder. In one embodiment, the therapeutic composition comprises at least one therapeutic agent to reducing at least one symptom associated with the patient’s disease or disorder. Exemplary therapeutic agents that can be administered to subjects identified as having or at increased risk of developing an autoimmune disease or disorder include, but are not limited to, immunosuppressant drugs including, but not limited to, corticosteroids (e.g., prednisone, budesonide, and prednisolone), tofacitinib, calcineurin inhibitors (e.g., tacrolimus and cyclosporine), antiproliferative agents (e.g., mycophenolate mofetil, mycophenolate sodium, leflunomide and azathioprine), mTOR inhibitors (e.g., sirolimus and everolimus), biologics (e.g., abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, ixekizumab, natalizumab, secukinumab, tacilizumab, ustekinumab, and vedolizumab) and monoclonal antibodies (e.g., basiliximab, daclizumab, and muromonab), hydroxychloroquine, methotrexate, cyclosporine, lifitegrast, nonsteroidal anti- inflammatory drugs, pilocarpine, and cevimeline. Therapeutic compositions can be administered to a subject in need in a wide variety of ways. In various embodiments, the therapeutic composition of the invention is administered orally, intraoperatively, intravenously, intravascularly, intramuscularly, subcutaneously, intracerebrally, intraperitoneally, by soft tissue injection, by surgical placement, by arthroscopic placement, or by percutaneous insertion, e.g., direct injection, cannulation or catheterization. Any administration may be a single administration of a therapeutic composition or multiple administrations. Administrations may be to single site or to more than one site in the subject being treated. Multiple administrations may occur essentially at the same time or separated in time. Subjects to which administration of the pharmaceutical compositions of the invention is contemplated include, but are not limited to, humans and other primates, mammals including commercially relevant mammals such as non-human primates, cattle, pigs, horses, sheep, cats, and dogs. Pharmaceutical compositions of the present invention may be administered in a manner appropriate to the disease to be treated (or prevented). The quantity and frequency of administration will be determined by such factors as the condition of the subject, and the type and severity of the subject’s disease, although appropriate dosages may be determined by clinical trials. When “therapeutic amount” is indicated, the precise amount of the compositions of the present invention to be administered can be determined by a physician with consideration of individual differences in age, weight, disease type, extent of disease, and condition of the patient (subject). The administration of the subject compositions may be carried out in any convenient manner, including by aerosol inhalation, injection, ingestion, transfusion, implantation or transplantation. The compositions described herein may be administered to a patient subcutaneously, intradermally, intratumorally, intranodally, intramedullary, intramuscularly, by intravenous (i.v.) injection, or intraperitoneally. In one embodiment, the compositions of the present invention are administered to a patient by intradermal or subcutaneous injection. In another embodiment, the compositions of the present invention are preferably administered by i.v. injection. The therapeutic composition can be incorporated into any formulation known in the art. For example, the therapeutic composition may be incorporated into formulations suitable for oral, parenteral, intravenous, subcutaneous, percutaneous, topical, buccal, or another route of administration. Suitable compositions include, but are not limited to, tablets, capsules, caplets, pills, gel caps, troches, dispersions, suspensions, solutions, syrups, granules, beads, transdermal patches, gels, powders, pellets, magmas, lozenges, creams, pastes, plasters, lotions, discs, suppositories, liquid sprays for nasal or oral administration, dry powder or aerosolized formulations for inhalation, compositions and formulations for intravesical administration and the like. It should be understood that the formulations and compositions that would be useful in the present invention are not limited to the particular formulations and compositions that are described herein. Although the description of pharmaceutical compositions provided herein are principally directed to pharmaceutical compositions which are suitable for ethical administration to humans, it will be understood by the skilled artisan that such compositions are generally suitable for administration to animals of all sorts. Modification of pharmaceutical compositions suitable for administration to humans in order to render the compositions suitable for administration to various animals is well understood, and the ordinarily skilled veterinary pharmacologist can design and perform such modification with merely ordinary, if any, experimentation. Subjects to which administration of the pharmaceutical compositions of the invention is contemplated include, but are not limited to, humans and other primates, mammals including commercially relevant mammals such as non-human primates, cattle, pigs, horses, sheep, cats, and dogs. In the method of treatment, the administration of the composition of the invention may be for either “prophylactic” or “therapeutic” purpose. When provided prophylactically, the composition of the present invention is provided in advance of any sign or symptom, although in particular embodiments the invention is provided following the onset of at least one sign or symptom to prevent further signs or symptoms from developing or to prevent present signs or symptoms from becoming more severe. The prophylactic administration of the composition serves to prevent or ameliorate subsequent signs or symptoms. When provided therapeutically, the pharmaceutical composition is provided at or after the onset of at least one sign or symptom. Thus, the present invention may be provided either prior to the anticipated exposure to a disease-causing agent or disease state or after the initiation of the disease or disorder. Kits The present invention further includes an assay kit containing the electrochemical sensor array and instructions for the set-up, performance, monitoring, and interpretation of the assays of the present invention. Optionally, the kit may include reagents for the detection of one or more autoantibody subclass. The kit may also optionally include the sensor reader. EXPERIMENTAL EXAMPLES The invention is further described in detail by reference to the following experimental example. This example is provided for purposes of illustration only, and is not intended to be limiting unless so specified. Thus, the invention should in no way be construed as being limited to the following example, but rather, should be construed to encompass any and all variations which become evident as a result of the teaching provided herein. Without further description, it is believed that one of ordinary skill in the art can, using the preceding description and the following illustrative examples, make and utilize the present invention and practice the claimed methods. The following working example, therefore, specifically points out exemplary embodiments of the present invention, and is not to be construed as limiting in any way the remainder of the disclosure. Example 1: Detecting the presence of polymeric and monomeric IgA1 anti-SSA/Ro Primary Sjögren's disease (pSD) is an autoimmune disease that attacks the exocrine glands, particularly the lacrimal and salivary glands through lymphocytic infiltration, leading to symptoms of ocular and oral dryness due to glandular dysfunction (Fox RI.2005, Lancet;366:321–331). It is the second most common systemic autoimmune rheumatic (or connective tissue) disease after rheumatoid arthritis (RA) (Nocturne G, Mariette X.2013, Nat Rev Rheumatol;9:544–556). SICCA syndrome patients are also characterized by dysfunctional secretory glands but in the absence of autoimmune features such as autoantibody production or lymphocytic infiltrates in the affected glands (Chen K-S, Jiang M-C, Li C-J, Liu O-K, Tsai C-SS. J Int Med Res 2009;37:1088–1096). Based on the most recent 2016 ACR/EULAR classification, a total score 4 is needed to meet the criteria for primary SD (Fox RI.2005, Lancet;366:321–331). The production of serum IgG autoantibodies to SSA/Ro and lymphocytic infiltrates of minor salivary glands are key autoimmune features of pSD. However, it is unclear which key factor is responsible secretory gland destruction and orchestrate pSD disease progression (Nocturne G, Mariette X.2013, Nat Rev Rheumatol;9:544–556). From translational studies, signatures of aberrant immune responses in pSD include: 1) the presence of type I interferons (IFNs)( Nocturne G, Mariette X.2013, Nat Rev Rheumatol;9:544–556; Nezos A, Gravani F, Tassidou A, Kapsogeorgou EK, Voulgarelis M, Koutsilieris M, et al.2015, J Autoimmun 2015;63:47–58; Li H, Ice JA, Lessard CJ, Sivils KL.2013, Front Immunol;4:290); 2) elevated serum follicular helper T cells in pSD (Jin L, Yu D, Li X, Yu N, Li X, Wang Y, et al.2014, Int J Clin Exp Pathol;7:1988–1996; Li X, Wu Z, Ding J, Zheng Z, Li X, Chen L, et al.2012, Biochem Biophys Res Commun;422:238–244); 3) marked elevation of serum IgG, IgA, and IgM (Gumpel JM, Hobbs JR. Serum immune globulins in Sjögren’s disease. Ann Rheum Dis 1970;29:681–683); and 4) marked B-cell activation processes with increased frequency of B-cell lymphomas (Hildebrand JM, Luo Z, Manske MK, Price-Troska T, Ziesmer SC, Lin W, et al.2010, J Exp Med;207:2569–2579; Thompson N, Isenberg DA, Jury EC, Ciurtin C. 2016, Rheumatology (Oxford) 2016;55:1548–1555; Alunno A, Leone MC, Giacomelli R, Gerli R, Carubbi F.2018, Front Med (Lausanne);5:102). In a study of paired serum and saliva antibody profile in 15 Sjögren's disease patients found 8 had IgG and IgM anti- SSA/Ro, 6 had IgG and IgM anti-SSB/La, and only 1 had IgA anti-SSA/Ro in serum. In saliva, 8 had IgG and IgA anti-SSA/Ro, and 6 for IgG and IgA anti-SSB/La, and negative for IgM anti-SSA/Ro and anti-SSB/La (Ben-Chetrit E, Fischel R, Rubinow A.1993, Clin Rheumatol;12:471–474). This finding suggests that IgA class autoantibodies are synthesized primarily in the salivary gland and can be detected in saliva before emerging in the serum. Therefore, local production and deposition of IgA within salivary glands may contribute toward secretory gland destruction and may contribute to the pathogenesis of pSD. IgA is abundant in the mucosal secretions and serum, playing a significant pathogenic role as the first line of defense in many mucosal surfaces. IgA exists in two isotypes (subtypes): IgA1, which predominates in serum; and IgA2, which predominates in secretions (Kerr MA.1990, Biochem J;271:285–296). IgA1 can further be subdivided into monomeric and polymeric subclasses (Monteiro RC.2010, J Clin Immunol;30:1–9). Human serum IgA1 mostly exists as monomeric form (85-90%), and with minor component as polymeric form. Monomeric and polymeric IgA1 (mIgA1 and pIgA1) are structurally different due to the presence of galactose in the monomeric IgA1, and absence in the polymeric IgA1 (Kerr MA.1990, Biochem J;271:285–296; Kondoh H, Kobayashi K, Hagiwara K.1987, Mol Immunol;24:1219–1222; Oortwijn BD, Roos A, Royle L, Gijlswijk- Janssen DJ van, Faber-Krol MC, Eijgenraam J-W, et al.2006, JASN;17:3529–3539). The presence of galactose in mIgA1 can be detected using the galactose-specific legume lectin erythrina cristagalli (ECL) (Turton K, Natesh R, Thiyagarajan N, Chaddock JA, Acharya KR.2004, Glycobiology;14:923–929). Polymeric IgA1 also has the presence of J chain, and not in monomeric (Kerr MA.1990, Biochem J;271:285–296). In addition to structural differences, mIgA1 and pIgA1 also exhibit differential immunoregulatory roles as immune suppressor and inducer respectively. Serum mIgA1 is a powerful anti-inflammatory effector toward the immune system (Monteiro RC. 2010, J Clin Immunol;30:1–9; Oortwijn BD, Roos A, Royle L, Gijlswijk-Janssen DJ van, Faber-Krol MC, J-W, et al.2006, JASN;17:3529–3539). The IgA receptor _{(Fc RI)} I_{gA2. Binding of mIgA1 leads to Fc RI-mediated inhibition of} immune responses. In contrast, highly multimeric serum IgA or circulating IgA immune complexes interaction induced an activating signal. IgA nephropathy is characterized by mesangial deposition of pIgA1 which may recruit lectins of the inflammatory pathway (Oortwijn BD, Roos A, Royle L, Gijlswijk-Janssen DJ van, Faber-Krol MC, Eijgenraam J- W, et al.2006, JASN;17:3529–3539) but the role of mIgA1 in an autoimmune disorder has not been established. Therefore, in this study, IgA subtype and subclasses were characterized in saliva supernatant of pSD, SICCA, and healthy cohorts and correlate findings to lymphocytic infiltrates of minor salivary glands (focus scores), supporting possible role in the pathogenesis of Sjögren’s disease. The materials and methods used in the experiments are now described. Patients This prospective cohort included 34 patients fulfilling the American College of Rheumatology (ACR) Classification Criteria for Sjögren’s disease (Shiboski S, Shiboski C, Criswell L, Baer A, Challacombe S, Lanfranchi H, et al.2012, Arthritis Care Res (Hoboken);64:475–487) and 35 patients who had SICCA symptoms, but did not fulfil the classification criteria for pSD (designated SICCA). All patients were evaluated at the Rheumatology Clinic at Seoul National University Hospital for diagnostic work-up (Table 1). Forty-one age- and gender-matched healthy control subjects with no history of autoimmune disease were included. Written informed consent was obtained from all participants. Table 1. Demographic characteristics of pSD and SICCA patients. Values are given in mean and standard deviation and positive in numbers of patients. Statistical significance was achieved if the P-value was <0.05. pSD SICCA P-value (n = 34) (n = 35) ^{Age (years)} _{54.0 10.5 57.8 14.5} ^0.207 Female 34/34 31/35 0.116 Symptom duration (months) 46.1 53.5 47.0 83.4 0.960 Ocular dryness 28/33 32/35 0.471 Oral dryness 29/33 29/33 1.000 Unstimulated whole saliva flow 6/9 - - rate 0.10 ml/min Labial salivary gland focus score 22/27 1/29 <0.001 1 foci/4 mm Keratoconjunctivitis SICCA 31/34 21/35 0.005 Positive ANA 30/34 12/35 <0.001 Positive serum SSA/Ro 29/34 0/35 <0.001 autoantibody Positive serum SSB/La 22/34 0/35 <0.001 autoantibody Saliva collection Unstimulated whole saliva samples were collected for 15 minutes as previously described (Hu S, Wang J, Meijer J, Ieong S, Xie Y, Yu T, et al.2007, Arthritis Rheum;56:3588–3600). The samples were kept on ice and centrifuged immediately after collection at 2600 g for 15 minutes at 4 ºC. The supernatant was supplemented with 1 L aprotinin (stock 10 mg/mL; Sigma-Aldrich Corp., St. Louis, MO), 3 L Na3VO4 (stock 400 mM; Fivephoton Biochemicals, San Diego, CA), and 10 L phenylmethylsulfonyl fluoride (stock 10 mg/mL; Sigma-Aldrich Corp., St. Louis, MO) and stored at -80 ºC until analysis. For analysis, the saliva samples were thawed and vortexed for 10 seconds. EFIRM immunoassay The EFIRM immunoassay was developed to detect salivary anti-SSA/Ro-52 autoantibodies using recombinant human SSA/Ro-52 polymerized onto the gold surface of EFIRM electrodes (Figure 1). The 52-kDa SSA subunit was chosen as an antigen target to capture salivary anti-SSA/Ro-52 autoantibodies because anti-SSA/Ro-52 has the highest positive predictive value (100%) compared to that of anti-SSA/Ro-60 (25%) in serum (Theander E, Jonsson R, Sjöström B, Brokstad K, Olsson P, Henriksson G.2015, Arthritis & Rheumatology;67:2427– 2436). Assay for detection of salivary SSA/Ro-52 autoantibodies was optimized using human anti-SSA/Ro-52 (Lifespan Biosciences Inc., Seattle, WA) to generate an optimal calibration curve. The following secondary antibodies were used for each isotype detection: IgG/M/A (H+L) goat anti-human biotin (Invitrogen^TM, Carlsbad, CA), biotinylated polyclonal anti- human IgG (H+L) (Thermo Fisher Scientific, Waltham, MA), biotin anti-human IgA rabbit monoclonal antibody (RevMab Biosciences, South San Francisco, CA), rabbit anti-human IgA1 recombinant secondary antibody, biotin (Thermo Fisher Scientific, Waltham, MA), rabbit anti-human IgA2 recombinant secondary antibody, biotin (Thermo Fisher Scientific, Waltham, MA), and ECL biotinylated (Vector Laboratories, Newark, CA). Polymeric IgA1 was determined by subtracting measurements of ECL from that of IgA1. Clinical samples (n = 110) were blinded and assayed in a randomization design to ensure that saliva samples from patients with pSD, patients with SICCA, and healthy control subjects were evenly distributed across the experimental runs. The experiments were run in duplicate, and the result was obtained by taking the geometric mean across the duplicates. Statistical analysis Patient demographic characteristics of pSD and SICCA and study variables _{were summarized using mean ( standard deviation) for continuous variables or frequency.} Level of salivary immunoglobulins (IgG/M/A, IgG, IgA, IgA1, and IgA2) in patients of pSD and SICCA and health controls were assessed via Wilcoxon t-test. Statistical significance was achieved if the P-value was <0.05. The discriminatory performance of anti-SSA/Ro-52 autoantibodies measured in saliva was assessed using the area under the receiver operating characteristic curves (AUC). The associated 95% confidence interval was constructed using DeLong’s method to estimate the variance (DeLong ER, Peterson ED, DeLong DM, Muhlbaier LH, Hackett S, Mark DB.1997, Stat Med;16:2645–2664). In order to propose an exploratory multivariable model for discriminating SICCA from pSD patients, Classification and Regression Tree Model (CART) (James G, Witten D, Hastie T, Tibshirani R.2014, An Introduction to Statistical Learning: With Applications in R) was implemented by inputting six potential markers as potential predicators (IgG, IgA, IgA1, IgA2, mIgA1, and pIgA1). Statistical analyses were run using Wilcoxon t-test and CART models were constructed using R V4.1.0 (www. r-project.org, Vienna, AU) and p-values <0.05 were considered statistically significant. Distribution of IgA1 subclasses in SICCA and pSD patients were visualized using scatter plot of IgA1 (y-axis) and mIgA1 (x-axis) with cut-off values from the CART model. To assess the correlation between immunoglobulin isotypes and focus score, Pearson correlation coefficients were computed. Z-scores were computed by obtaining the overall mean for each marker (mIgA1 and pIgA1) and dividing by their respective standard deviations. Summary of data of focus score, serum immunoglobulin, and saliva immunoglobulin in pSD, SICCA, and healthy control were listed. The experimental results are now described Baseline characteristics of patients Thirty-four patients with pSD and 35 patients with SICCA syndrome were enrolled (Table 1). The study population was predominantly female (94%), and the mean age (± SD) was 54.6 ± 10.5 years in the pSD group and 57.3 ± 14.5 years in the SICCA group. The distribution of symptoms of oral and ocular dryness did not differ between the groups. More pSD patients had a detectable antinuclear antibody titre (ANA) than did the SICCA patients (88.2% vs 34.3%, P < 0.001). Serum SSA/Ro-52 and SSB/La autoantibodies were present in 85.3% (29/34) and 64.7% (22/34) of the patients with pSD respectively, whereas none of the SICCA patients had detectable serum SSA/Ro-52 or SSB/La autoantibodies. Histological analysis of the labial salivary gland biopsies from the patients with SICCA did not reveal presence of histopathological changes (i.e., focus score <1) (Fisher BA, Jonsson R, Daniels T, Bombardieri M, Brown RM, Morgan P, et al.2017, Ann Rheum Dis;76:1161– 1168). Focus score 1 was present in 22 (81.5%) of 27 pSD patients. Keratoconjunctivitis SICCA (Baldini C, Talarico R, Tzioufas AG, Bombardieri S.2012 J Autoimmun;39:9–14), _{defined as positive Schirmer test ( 5 mm of strip is wet after 5 minutes) and/or ocular} staining score 5 or van Bijsterveld score 4, in at least one eye, was more common in the pSD than the SICCA patients (91.2% vs.60.0%, P = 0.005) (Table 1). Salivary anti-SSA/Ro-52 autoantibody as a biomarker to discriminate pSD, SICCA patients, and healthy subjects The potential of each salivary immunoglobulin isotypes to SSA/Ro-52 autoantibody was explored as a biomarker to differentiate pSD patients, SICCA patients, and healthy control subjects. First, the nonparametric Wilcoxon t-test was performed for anti- SSA/Ro-52 isotypes IgG/M/A, IgG, IgA, IgA1, or IgA2. They were all statistically significant (P <0.003) among pSD, SICCA, and control groups for all isotypes, with the exception of IgA, and IgA2 were not significant between pSD, and SICCA (Figure 2). Secondly, performance of IgG/M/A assay was evaluated by the area under the ROC curve (AUC): pSD vs SICCA, 0.81 (95% CI: 0.7070–0.9141) (Figure 3A); SICCA vs control, 0.88 (95% CI: 0.8111–0.9547) (Figure 3B); pSD vs control, 0.98 (95% CI: 0.9595– 1.0) (Figure 3C); and combined pSD and SICCA vs control, 0.93 (95% CI: 0.8906–0.9751) (Figure 3D). IgG/M/A assay can distinguish between pSD, SICCA, and control groups. CART model of immunoglobulin IgA SSA/Ro-52 isotypes as potential predictors to discriminate SICCA from pSD patients CART model that selects variables and cut-points by using recursive partitioning to discriminate healthy, pSD, and SICCA groups by combining six chosen predicators (IgG, IgA, IgA1, IgA2, mIgA1, and pIgA1) (Figure 4). The overall accuracy of the cart model is 78.2% with sensitivity of 82.4% (28/34) for predicting pSD and 71.43% (25/35) for predicting SICCA. The specificity for neither pSD nor SICCA is 80.9% (33/41). Distribution of subclasses of anti-SSA/Ro-52 IgA1 (mIgA1 and pIgA1) in SICCA and pSD patients To visualize the distribution of subclasses of IgA1, a scatterplot of two variables, mIgA1 and pIgA1, was constructed with color-coded points by SICCA and pSD groups (Figure 5). To select potential cut-points in a data driven way to best separate groups, a CART model was run. The CART model selected a cut-point at 339 pIgA1 and 191 mIgA1 which split the data into three distinct clusters (Figure 5). Elevated mIgA1 was observed in SICCA patients while elevated pIgA1 was observed in pSD patients. The classification accuracy of group status across these clusters was 80% indicating that there is an association between these markers (monomeric vs polymeric IgA1) and SICCA vs pSD. This could be further demonstrated in Figure 6, where Z score for pIgA1, and mIgA1 were plotted for patients with pSD, SICCA, and control. It was found that pIgA1 was significantly different between pSD and SICCA (p<.001), and mIgA1 was different in SICCA, and pSD (p<.023). It clearly demonstrated that prevalence of mIgA1 in SICCA, and pIgA1 in pSD. Pearson correlation coefficient between immunoglobulin isotypes and focus score Histological analysis of the labial salivary gland biopsies allowed the calculation of focus scores, determined by the number of mononuclear cell infiltrates containing at least 50 inflammatory cells in a 4 mm² glandular section (Fisher BA, Jonsson R, Daniels T, Bombardieri M, Brown RM, Morgan P, et al.2017, Ann Rheum Dis;76:1161– 1168). To determine the correlation of histopathological changes (i.e., focus score >1) and immunoglobulin isotypes to SSA/Ro-52, Pearson correlation coefficient model was used. The Pearson correlation to focus score is 0.385**, P-value = 0.004 for polymeric IgA1; 0.358**, P-value = 0.007 for IgG; 0.306*, P-value = 0.023 for IgA; while mIgA1 is not correlated with focus score. (Table 2). However, since all three of these biomarkers are also correlated with each other, they may not be providing independently significant information for predicting the degree of focal lymphocytic infiltration (foci) in the labial salivary gland tissue in a multivariable model. Table 2. Pearson correlation coefficients between immunoglobulin isotypes and focus score pathogenesis. Four isotypes were significantly associated with focus score (IgA1, IgG, and polymeric IgA1). Statistical significance was achieved if the P-value was <0.05, *, 2-tailed and <0.01, **, 2-tailed. Focus IgA1 IgA2 IgA IgG Monomeric Polymeric Score - EFIRM EFIRM EFIRM EFIRM IgA1 IgA1 ID Focus Score Pearson 1 .345^** -0.076 0.192 .358^** -0.177 .467^** -ID p-value 0.010 0.580 0.159 0.007 0.196 0.000 N 55 55 55 55 55 55 55 IgA1 Pearson .345^** 1 .467^** .800^** .682^** .338^** .708^** EFIRM p-value 0.010 0.000 0.000 0.000 0.004 0.000 N 55 69 69 69 69 69 69 IgA2 Pearson -0.076 .467^** 1 .711^** 0.235 .641^** -0.032 EFIRM p-value 0.580 0.000 0.000 0.052 0.000 0.797 N 55 69 69 69 69 69 69 IgA EFIRM Pearson 0.192 .800^** .711^** 1 .569^** .472^** .415^** p-value 0.159 0.000 0.000 0.000 0.000 0.000 N 55 69 69 69 69 69 69 IgG EFIRM Pearson .358^** .682^** 0.235 .569^** 1 0.089 .589^** p-value 0.007 0.000 0.052 0.000 0.466 0.000 N 55 69 69 69 69 69 69 Monomeric Pearson -0.177 .338^** .641^** .472^** 0.089 1 -.425^** IgA1 p-value 0.196 0.004 0.000 0.000 0.466 0.000 N 55 69 69 69 69 69 69 Polymeric Pearson .467^** .708^** -0.032 .415^** .589^** -.425^** 1 IgA1 p-value 0.000 0.000 0.797 0.000 0.000 0.000 N 55 69 69 69 69 69 69 Serum monomeric IgA1 in serum had been known to control the immune system by inhibiting inflammatory response, and development of asthma and glomerulonephritis (Monteiro RC.2010, J Clin Immunol;30:1–9) . Configurations (activating vs inhibitory) were dependent on the way the tyrosine-based activation motifs (ITAM) containing receptor interacted with its ligand. Delacroix et al. observed an increase of total IgA1 and pIgA1 in serum of patients with pSD (Delacroix et al., 1983, J. Clin. Invest;71:358-367), with unknown antigen. In this study, a marked elevation of autoantibody pIgA1 against SSA/Ro-52 was found in pSD patients while a marked elevation of mIgA1 anti-SSA/Ro-52 was found in SICCA patients (Figures 5 & 6). This finding shows that autoantibody IgA1 SSA/Ro-52 with a difference in subclass between monomeric and polymeric form differentiates between SICCA versus pSD autoimmune disease. The disclosures of each and every patent, patent application, and publication cited herein are hereby incorporated herein by reference in their entirety. While this invention has been disclosed with reference to specific embodiments, it is apparent that other embodiments and variations of this invention may be devised by others skilled in the art without departing from the true spirit and scope of the invention. The appended claims are intended to be construed to include all such embodiments and equivalent variations. Embodiments The following clauses describe particular Embodiments of the invention. 1. A system comprising a device for detecting the presence or relative level of at least one subclass of at least one autoantibody in a subject, comprising: an array of units on a substrate, each unit comprising an electrode chip including a working electrode, a counter electrode, and a reference electrode; wherein the working electrode of at least one unit is coated with a conducting polymer embedded or functionalized with at least one capture antigen, wherein at least one capture antigen is a target antigen of an autoantibody, and at least one secondary binding molecule, wherein the secondary binding molecule binds to a specific isotype of autoantibody or subclass of autoantibody. 2. The system of embodiment 1, wherein the secondary binding molecule is specific for the monomeric subclass of the autoantibody. 3. The system of embodiment 1 or 2, wherein the target antigen is the 52 kDa SSA subunit (Ro-52) or a fragment thereof. 4. The system of any one of embodiments 1 to 3, wherein the target antigen is the 60 kDa SSA subunit (Ro-60) or a fragment thereof. 5. The system of any one of embodiments 1 to 4, wherein the secondary binding molecule is specific for the IgM, IgD, IgG, IgE, IgA, IgA1, or IgA2 isotype of the autoantibody. 6. The system of any one of embodiments 1 to 5, wherein the secondary binding molecule is erythrina cristagalli lectin that specifically detects only monomeric IgA1. 7. The system of any one of embodiments 1 to 6, wherein the secondary binding molecule is specific for the monomeric or polymeric subclass of an anti-SSA/Ro autoantibody. 8. The system of any one of embodiments 1 to 8, wherein the secondary binding molecule is specific for the monomeric or polymeric subclass of an IgA1 anti-SSA/Ro autoantibody. 9. A method of detecting at least one specific subclass or isotype of an autoantibody in a subject comprising: obtaining a saliva sample from the subject; adding a first portion of the sample mixture to an electrode chip on a device comprising an array of units on a substrate, each unit comprising an electrode chip including a working electrode, a counter electrode, and a reference electrode; wherein the working electrode of at least one unit is coated with a conducting polymer embedded or functionalized with at least one capture antigen, wherein at least one capture antigen is a target antigen of an autoantibody; contacting the sample with a secondary binding molecule, wherein the secondary binding molecule binds to the specific isotype of autoantibody or subclass of autoantibody, or a combination thereof, and further wherein the secondary binding molecule is linked to a detectable moiety for generating a current; and measuring the current in the electrode chip, wherein a change in current is correlated to the presence of the specific subclass of the autoantibody in the sample. 10. The method of embodiment 9, wherein the secondary binding molecule is specific for the monomeric subclass of the autoantibody. 11. The method of embodiment 9 or 10, wherein the secondary binding molecule is specific for the IgM, IgD, IgG, IgE, IgA, IgA1, or IgA2 isotype of the autoantibody. 12. The method of any one of embodiments 9 to 11, wherein the secondary binding molecule is erythrina cristagalli lectin that specifically detects only monomeric IgA1. 13. The method of any one of embodiments 9 to 12, wherein the target antigen is the 52 kDa SSA subunit (Ro-52) or a fragment thereof. 14. The method of any one of embodiments 9 to 13, wherein the target antigen is the 60 kDa SSA subunit (Ro-60) or a fragment thereof. 15. The method of any one of embodiments 9 to 14, wherein the secondary binding molecule is specific for the monomeric subclass of an anti-SSA/Ro autoantibody. 16. The method of any one of embodiments 9 to 15, wherein the secondary binding molecule is specific for the monomeric subclass of an IgA1 anti-SSA/Ro autoantibody. 17. A method of diagnosing a disease associated with at least one specific subclass or isotype of an autoantibody in a subject comprising: obtaining a saliva sample from the subject; adding a first portion of the sample mixture to an electrode chip on a device comprising an array of units on a substrate, each unit comprising an electrode chip including a working electrode, a counter electrode, and a reference electrode; wherein the working electrode of at least one unit is coated with a conducting polymer embedded or functionalized with at least one capture antigen, wherein at least one capture antigen is a target antigen of an autoantibody; contacting the sample with a secondary binding molecule, wherein the secondary binding molecule binds to the specific isotype of autoantibody or subclass of autoantibody, or a combination thereof, and further wherein the secondary binding molecule is linked to a detectable moiety for generating a current; and measuring the current in the electrode chip, wherein a change in current is correlated to the presence of the specific subclass of the autoantibody in the sample. 18. The method of embodiment 17, wherein the secondary binding molecule is specific for the monomeric subclass of the autoantibody. 19. The method of embodiment 17 or 18, wherein the secondary binding molecule is specific for the IgM, IgD, IgG, IgE, IgA, IgA1, or IgA2 isotype of the autoantibody. 20. The method of any one of embodiments 17 to 19, wherein the secondary binding molecule is molecule is erythrina cristagalli lectin that specifically detects only monomeric IgA1. 21. The method of any one of embodiments 17 to 20, wherein the target antigen is the 52 kDa SSA subunit (Ro-52) or a fragment thereof. 22. The method of any one of embodiments 17 to 21, wherein the target antigen is the 60 kDa SSA subunit (Ro-60) or a fragment thereof. 23. The method of any one of embodiments 17 to 22, wherein the secondary binding molecule is specific for the monomeric subclass of an anti-SSA/Ro autoantibody. 24. The method of any one of embodiments 17 to 23, wherein the secondary binding molecule is specific for the monomeric subclass of an IgA1 anti-SSA/Ro autoantibody. 25. A method of differentially diagnosing a subject as having or being at increased risk of primary Sjögren’s disease (pSD) or SICCA syndrome disease, the method comprising: obtaining a saliva sample from a subject identified as being at risk of SICCA or pSD; detecting the total IgA1 anti-SSA/Ro autoantibody in the sample; calculating the level or relative amount of at least one of the monomeric or polymeric subclass of the IgA1 type anti-SSA/Ro autoantibody in the sample from the difference in the level of the measured monomeric or polymeric subclass of the IgA1 type anti-SSA/Ro autoantibody in the sample and the detected total IgA1 type anti-SSA/Ro autoantibody in the sample; comparing the level or amount of at least one of the monomeric or polymeric subclass of the IgA1 anti-SSA/Ro autoantibody in the sample to a comparator control; and diagnosing the subject as having or being at risk of SICCA when an increased level of the monomeric IgA1 anti-SSA/Ro autoantibody is identified or diagnosing the subject as having or being at risk of pSD when an increased level of the polymeric IgA1 anti-SSA/Ro autoantibody is identified as compared to the comparator control. 26. The method of embodiment 25 further comprising: obtaining a saliva sample from a subject identified as being at risk of SICCA or pSD; adding a first portion of the sample mixture to an electrode chip on a device comprising an array of units on a substrate, each unit comprising an electrode chip including a working electrode, a counter electrode, and a reference electrode; wherein the working electrode of at least one unit is coated with a conducting polymer embedded or functionalized with at least one capture antigen, wherein at least one capture antigen comprises the 52 kDa SSA subunit (Ro52); contacting the sample with a secondary binding molecule, wherein the secondary binding molecule is specific for the monomeric or polymeric subclass of an IgA1 anti- SSA/Ro autoantibody, and further wherein the secondary binding molecule is linked to a detectable moiety for generating a current; and measuring the current in the electrode chip, wherein a change in current is correlated to the level or amount of the monomeric or polymeric subclass of the IgA1 anti-SSA/Ro autoantibody in the sample. 27. The method of embodiment 25 or 26, wherein the comparator control is at least one selected from the group consisting of: an established cut-point, a positive control, a negative control, a historical control, a historical norm, a control subject, and the level of a reference molecule in the biological sample. 28. The method of any one of embodiments 25 to 27, further comprising administering a therapeutic treatment for SICCA or pSD to the subject.

Claims

CLAIMS 1. A system comprising a device for detecting the presence or relative level of at least one subclass of at least one autoantibody in a subject, comprising: an array of units on a substrate, each unit comprising an electrode chip including a working electrode, a counter electrode, and a reference electrode; wherein the working electrode of at least one unit is coated with a conducting polymer embedded or functionalized with at least one capture antigen, wherein at least one capture antigen is a target antigen of an autoantibody, and at least one secondary binding molecule, wherein the secondary binding molecule binds to a specific isotype of autoantibody or subclass of autoantibody.

2. The system of claim 1, wherein the secondary binding molecule is specific for the monomeric subclass of the autoantibody.

3. The system of claim 1, wherein the target antigen is the 52 kDa SSA subunit (Ro- 52) or a fragment thereof.

4. The system of claim 1, wherein the target antigen is the 60 kDa SSA subunit (Ro- 60) or a fragment thereof.

5. The system of claim 1, wherein the secondary binding molecule is specific for the IgM, IgD, IgG, IgE, IgA, IgA1, or IgA2 isotype of the autoantibody.

6. The system of claim 1, wherein the secondary binding molecule is erythrina cristagalli lectin that specifically detects only monomeric IgA1.

7. The system of claim 1, wherein the secondary binding molecule is specific for the monomeric or polymeric subclass of an anti-SSA/Ro autoantibody.

8. The system of claim 1, wherein the secondary binding molecule is specific for the monomeric or polymeric subclass of an IgA1 anti-SSA/Ro autoantibody.

9. A method of detecting at least one specific subclass or isotype of an autoantibody in a subject comprising: obtaining a saliva sample from the subject; adding a first portion of the sample mixture to an electrode chip on a device comprising an array of units on a substrate, each unit comprising an electrode chip including a working electrode, a counter electrode, and a reference electrode; wherein the working electrode of at least one unit is coated with a conducting polymer embedded or functionalized with at least one capture antigen, wherein at least one capture antigen is a target antigen of an autoantibody; contacting the sample with a secondary binding molecule, wherein the secondary binding molecule binds to the specific isotype of autoantibody or subclass of autoantibody, or a combination thereof, and further wherein the secondary binding molecule is linked to a detectable moiety for generating a current; and measuring the current in the electrode chip, wherein a change in current is correlated to the presence of the specific subclass of the autoantibody in the sample.

10. The method of claim 9, wherein the secondary binding molecule is specific for the monomeric subclass of the autoantibody.

11. The method of claim 9, wherein the secondary binding molecule is specific for the IgM, IgD, IgG, IgE, IgA, IgA1, or IgA2 isotype of the autoantibody.

12. The method of claim 9, wherein the secondary binding molecule is erythrina cristagalli lectin that specifically detects only monomeric IgA1.

13. The method of claim 9, wherein the target antigen is the 52 kDa SSA subunit (Ro- 52) or a fragment thereof.

14. The method of claim 9, wherein the target antigen is the 60 kDa SSA subunit (Ro- 60) or a fragment thereof.

15. The method of claim 9, wherein the secondary binding molecule is specific for the monomeric subclass of an anti-SSA/Ro autoantibody.

16. The method of claim 9, wherein the secondary binding molecule is specific for the monomeric subclass of an IgA1 anti-SSA/Ro autoantibody.

17. A method of diagnosing a disease associated with at least one specific subclass or isotype of an autoantibody in a subject comprising: obtaining a saliva sample from the subject; adding a first portion of the sample mixture to an electrode chip on a device comprising an array of units on a substrate, each unit comprising an electrode chip including a working electrode, a counter electrode, and a reference electrode; wherein the working electrode of at least one unit is coated with a conducting polymer embedded or functionalized with at least one capture antigen, wherein at least one capture antigen is a target antigen of an autoantibody; contacting the sample with a secondary binding molecule, wherein the secondary binding molecule binds to the specific isotype of autoantibody or subclass of autoantibody, or a combination thereof, and further wherein the secondary binding molecule is linked to a detectable moiety for generating a current; and measuring the current in the electrode chip, wherein a change in current is correlated to the presence of the specific subclass of the autoantibody in the sample.

18. The method of claim 17, wherein the secondary binding molecule is specific for the monomeric subclass of the autoantibody.

19. The method of claim 17, wherein the secondary binding molecule is specific for the IgM, IgD, IgG, IgE, IgA, IgA1, or IgA2 isotype of the autoantibody.

20. The method of claim 17, wherein the secondary binding molecule is molecule is erythrina cristagalli lectin that specifically detects only monomeric IgA1.

21. The method of claim 17, wherein the target antigen is the 52 kDa SSA subunit (Ro-52) or a fragment thereof.

22. The method of claim 17, wherein the target antigen is the 60 kDa SSA subunit (Ro-60) or a fragment thereof.

23. The method of claim 17, wherein the secondary binding molecule is specific for the monomeric subclass of an anti-SSA/Ro autoantibody.

24. The method of claim 17, wherein the secondary binding molecule is specific for the monomeric subclass of an IgA1 anti-SSA/Ro autoantibody.

25. A method of differentially diagnosing a subject as having or being at increased risk of primary Sjögren’s disease (pSD) or SICCA syndrome disease, the method comprising: obtaining a saliva sample from a subject identified as being at risk of SICCA or pSD; detecting the total IgA1 anti-SSA/Ro autoantibody in the sample; calculating the level or relative amount of at least one of the monomeric or polymeric subclass of the IgA1 type anti-SSA/Ro autoantibody in the sample from the difference in the level of the measured monomeric or polymeric subclass of the IgA1 type anti-SSA/Ro autoantibody in the sample and the detected total IgA1 type anti-SSA/Ro autoantibody in the sample; comparing the level or amount of at least one of the monomeric or polymeric subclass of the IgA1 anti-SSA/Ro autoantibody in the sample to a comparator control; and diagnosing the subject as having or being at risk of SICCA when an increased level of the monomeric IgA1 anti-SSA/Ro autoantibody is identified or diagnosing the subject as having or being at risk of pSD when an increased level of the polymeric IgA1 anti-SSA/Ro autoantibody is identified as compared to the comparator control.

26. The method of claim 25 further comprising: obtaining a saliva sample from a subject identified as being at risk of SICCA or pSD; adding a first portion of the sample mixture to an electrode chip on a device comprising an array of units on a substrate, each unit comprising an electrode chip including a working electrode, a counter electrode, and a reference electrode; wherein the working electrode of at least one unit is coated with a conducting polymer embedded or functionalized with at least one capture antigen, wherein at least one capture antigen comprises the 52 kDa SSA subunit (Ro52); contacting the sample with a secondary binding molecule, wherein the secondary binding molecule is specific for the monomeric or polymeric subclass of an IgA1 anti-SSA/Ro autoantibody, and further wherein the secondary binding molecule is linked to a detectable moiety for generating a current; and measuring the current in the electrode chip, wherein a change in current is correlated to the level or amount of the monomeric or polymeric subclass of the IgA1 anti-SSA/Ro autoantibody in the sample.

27. The method of claim 25 or 26, wherein the comparator control is at least one selected from the group consisting of: an established cut-point, a positive control, a negative control, a historical control, a historical norm, a control subject, and the level of a reference molecule in the biological sample.

28. The method of claim 25 or 26, further comprising administering a therapeutic treatment for SICCA or pSD to the subject.