US20130052671A1 - Il-6 detection based early diagnosis and prediction of systematic inflammatory response syndrome and sepsis in asymptomatic patients - Google Patents

Il-6 detection based early diagnosis and prediction of systematic inflammatory response syndrome and sepsis in asymptomatic patients Download PDF

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Publication number
US20130052671A1
US20130052671A1 US13/601,787 US201213601787A US2013052671A1 US 20130052671 A1 US20130052671 A1 US 20130052671A1 US 201213601787 A US201213601787 A US 201213601787A US 2013052671 A1 US2013052671 A1 US 2013052671A1
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Prior art keywords
patient
sirs
level
variant
sample
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Abandoned
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US13/601,787
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English (en)
Inventor
Susanne Grueb
Freyja-Maria Smolle-Juettner
Nicole Neuboeck
Annelie-Martina Weinberg
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Medizinische Universitaet Graz
Roche Diagnostics Operations Inc
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Medizinische Universitaet Graz
Roche Diagnostics Operations Inc
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Publication of US20130052671A1 publication Critical patent/US20130052671A1/en
Assigned to MEDIZINISCHE UNIVERSITAET GRAZ reassignment MEDIZINISCHE UNIVERSITAET GRAZ ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: WEINBERG, ANNELIE-MARTINA, NEUBOECK, NICOLE, SMOLLE-JUETTNER, FREYJA-MARIA
Assigned to ROCHE DIAGNOSTICS GMBH reassignment ROCHE DIAGNOSTICS GMBH ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: GRUEB, SUSANNE
Assigned to ROCHE DIAGNOSTICS OPERATIONS, INC. reassignment ROCHE DIAGNOSTICS OPERATIONS, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ROCHE DIAGNOSTICS GMBH
Priority to US15/196,718 priority Critical patent/US11635438B2/en
Abandoned legal-status Critical Current

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
    • G01N33/6869—Interleukin
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/52—Assays involving cytokines
    • G01N2333/54—Interleukins [IL]
    • G01N2333/5412—IL-6
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/24—Immunology or allergic disorders
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/26—Infectious diseases, e.g. generalised sepsis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/50—Determining the risk of developing a disease

Definitions

  • a method for detecting the level of IL-6 in an asymptomatic patient for detection or diagnosis of a risk to develop or suffer from SIRS or sepsis comprising the steps of determining the level of IL-6 or a variant thereof in a sample from the patient and comparing the level of IL-6 or a variant thereof determined in the determining step to a reference level. According to various embodiments, based on the comparison it is detected or diagnosed if the patient is at risk to develop or suffer from SIRS or sepsis. In some embodiments, the sample is isolated at least 2 times at short intervals and the determining and comparing steps are repeated for each sample.
  • FIGS. 4 a - 4 d are a graph presenting CRP (mg/L) kinetics in asymptomatic patients pre- and post-surgery showing a comparison between pooled patients who developed SIRS/sepsis and those who did not (having CRP levels plotted for baseline 1 (pre-surgery), baseline 2 (during surgery), and post-surgery (day 1, 2, 3 and 4 in which samples were taken at 6 hour intervals) and having Median and the percentiles indicated).
  • FIG. 5 b is a graph presenting a comparison of the IL-6 kinetics (pg/ml) between pooled patients who developed SIRS/sepsis and those who did not (based on asymptomatic patients pre- and post-surgery).
  • a diagnosed infection is a additional diagnostic parameter generally required.
  • Methods for the detection or diagnosis of an infection are generally known in the field. The present disclosure provides that the risk to suffer from or develop sepsis may now be detected or diagnosed on the basis of only two parameters, i.e. a level of IL-6 above the reference level and a diagnosed infection.
  • asymptomatic patient encompasses a patient not displaying clinical signs and symptoms generally considered to establish diagnosis of SIRS.
  • the asymptomatic patient in general will display less than 2 symptoms and in some cases, less than 1 symptom of the following:
  • IL-6 may comprise the IL-6 which can be bound or which is bound by the antibody of Roche's IL-6 assay for use on Elecsys and cobas immunoassay systems (Roche).
  • IL-6 also encompasses a variant of the aforementioned IL-6, such as human IL-6.
  • the variant encompasses a protein or peptide substantially similar to the specific reference IL-6 molecule, such as the human IL-6.
  • the term substantially similar is well understood by the person skilled in the art.
  • the degree of identity between two amino acid sequences can be determined by algorithms well known in the art, for example. In general, the degree of identity is determined by comparing two optimally aligned sequences over a comparison window, where the fragment of amino acid sequence in the comparison window may comprise additions or deletions (e.g., gaps or overhangs) as compared to the reference sequence (which does not comprise additions or deletions) for optimal alignment.
  • the percentage can be calculated, for example, by determining the number of positions at which the identical amino acid residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the window of comparison and multiplying the result by 100 to yield the percentage of sequence identity.
  • determining the amount of an IL-6 peptide or polypeptide comprises the steps of (a) contacting a cell capable of eliciting a cellular response, the intensity of which is indicative of the amount of the peptide or polypeptide with the said peptide or polypeptide, for an adequate period of time, and (b) measuring the cellular response.
  • the sample or processed sample is, in some embodiments, added to a cell culture and an internal or external cellular response is measured.
  • the cellular response may include the measurable expression of a reporter gene or the secretion of a substance such as a peptide, polypeptide, or a small molecule.
  • the expression or substance may generate an intensity signal which correlates to the amount of the peptide or polypeptide.
  • determining the amount of a IL-6 peptide or polypeptide comprises the step of measuring a specific intensity signal obtainable from the peptide or polypeptide in the sample, for example in a sample selected from blood, serum, plasma or liquor.
  • a specific intensity signal may be the signal intensity observed at an m/z variable specific for the peptide or polypeptide observed in mass spectra or a NMR spectrum specific for the peptide or polypeptide.
  • Means for the detection of IL-6 are generally known in the art and preferably include anti-IL-6 antibodies, including polyclonal and monoclonal antibodies, as well as fragments thereof, such as Fv, Fab and F(ab)2 fragments that are capable of binding IL-6 antigen or hapten.
  • the means for the detection of IL-6 of the present disclosure also include single chain antibodies, chimeric, humanized hybrid antibodies wherein amino acid sequences of a non-human donor antibody exhibiting a desired antigen-specificity are combined with sequences of a human acceptor antibody.
  • an anti-IL-6 antibody from a mammalian species, such as an antibody selected from human, rat, mouse, goat, sheep, cattle, and camel.
  • Suitable measurement methods also include, for example, precipitation (particularly immunoprecipitation), electrochemiluminescence (electro-generated chemiluminescence), RIA (radioimmunoassay), ELISA (enzyme-linked immunosorbent assay), sandwich enzyme immune tests, electrochemiluminescence sandwich immunoassays (ECLIA), dissociation-enhanced lanthanide fluoro immuno assay (DELFIA), scintillation proximity assay (SPA), turbidimetry, nephelometry, latex-enhanced turbidimetry or nephelometry, or solid phase immune tests.
  • kit adapted for carrying out the method describe above, comprising:
  • kit refers to a collection of the aforementioned compounds, means or reagents of the present disclosure which may or may not be packaged together.
  • the components of the kit may be comprised by separate vials (i.e. as a kit of separate parts) or provided in a single vial.
  • the kit of the present disclosure is to be used for practising the methods referred to herein above.
  • all components are provided in a ready-to-use manner for practising the methods referred to above.
  • the kit may contain instructions for carrying out the said methods.
  • the instructions can be provided by a user's manual in paper or electronic form for example.
  • the manual may comprise instructions for interpreting the results obtained when carrying out the aforementioned methods using the kit of the present disclosure.
  • asymptomatic patient is a patient selected from the group of a trauma patient, a patient with burns, a patient undergoing an treatment, a patient undergoing an invasive treatment, a patient undergoing a surgical intervention.

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Cell Biology (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
US13/601,787 2010-03-02 2012-08-31 Il-6 detection based early diagnosis and prediction of systematic inflammatory response syndrome and sepsis in asymptomatic patients Abandoned US20130052671A1 (en)

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US15/196,718 US11635438B2 (en) 2010-03-02 2016-06-29 IL-6 detection based early diagnosis and prediction of systemic inflammatory response syndrome and sepsis in asymptomatic patients

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP10002190 2010-03-02
EP10002190.6 2010-03-02
PCT/EP2011/001006 WO2011116872A1 (fr) 2010-03-02 2011-03-02 Diagnostic et prédiction précoces, sur la base d'une détection il-6, d'un syndrome de réponse inflammatoire systémique et de septicémie chez des patients asymptomatiques

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PCT/EP2011/001006 Continuation WO2011116872A1 (fr) 2010-03-02 2011-03-02 Diagnostic et prédiction précoces, sur la base d'une détection il-6, d'un syndrome de réponse inflammatoire systémique et de septicémie chez des patients asymptomatiques

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US (2) US20130052671A1 (fr)
EP (1) EP2542894B1 (fr)
JP (1) JP5828849B2 (fr)
CN (1) CN102782501B (fr)
CA (1) CA2788636C (fr)
ES (1) ES2539854T3 (fr)
HK (1) HK1177963A1 (fr)
WO (1) WO2011116872A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
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US20070093721A1 (en) * 2001-05-17 2007-04-26 Lynn Lawrence A Microprocessor system for the analysis of physiologic and financial datasets
US20100079292A1 (en) * 1997-01-27 2010-04-01 Lawrence A. Lynn Microprocessor system for the analysis of physiologic and financial datasets
US9053222B2 (en) 2002-05-17 2015-06-09 Lawrence A. Lynn Patient safety processor
US9953453B2 (en) 2012-11-14 2018-04-24 Lawrence A. Lynn System for converting biologic particle density data into dynamic images
US10354753B2 (en) 2001-05-17 2019-07-16 Lawrence A. Lynn Medical failure pattern search engine
US10354429B2 (en) 2012-11-14 2019-07-16 Lawrence A. Lynn Patient storm tracker and visualization processor
US10540786B2 (en) 2013-02-28 2020-01-21 Lawrence A. Lynn Graphically presenting features of rise or fall perturbations of sequential values of five or more clinical tests

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Publication number Priority date Publication date Assignee Title
EP3572809A1 (fr) 2012-07-23 2019-11-27 Astute Medical, Inc. Procédés pour le diagnostic de la sepsie
CA2915611A1 (fr) * 2013-06-28 2014-12-31 Acumen Research Laboratories Pte. Ltd. Biomarqueurs du sepsis et leurs utilisations
EP3022314B1 (fr) 2013-07-15 2021-05-19 President and Fellows of Harvard College Dosages pour l'activité antimicrobienne et leurs applications
CN104634982B (zh) * 2013-11-06 2016-08-17 中国科学院上海生命科学研究院 Vegf-c在制备败血症及重症细菌感染诊断试剂中的用途
CN103969438B (zh) * 2014-04-29 2016-03-30 北京普恩光德生物科技开发有限公司 白介素6检测试剂盒
DE102014112924A1 (de) 2014-09-09 2016-03-10 Friedrich-Alexander-Universität Erlangen-Nürnberg Verfahren und System zur Detektion von Krankheitsbildern
DE102014112923A1 (de) 2014-09-09 2016-03-10 Friedrich-Alexander-Universität Erlangen-Nürnberg Verfahren und System zur Detektion von Krankheitsbildern
JP2023551542A (ja) 2020-11-30 2023-12-08 エニグマ バイオインテリジェンス，インコーポレイテッド アルツハイマー病の非侵襲的評価

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US20080114576A1 (en) * 2004-12-09 2008-05-15 Matthew Christo Jackson Early Detection of Sepsis

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JP2009229340A (ja) * 2008-03-25 2009-10-08 Sysmex Corp 全身性炎症反応症候群の重症度に関する情報を生成する方法及び装置
CN101393204A (zh) * 2008-10-16 2009-03-25 中山大学 血清il-6在制备原发性肝细胞癌诊断试剂盒中的应用

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US5882872A (en) * 1994-04-28 1999-03-16 Kudsk; Kenneth A. Use of an IL-6 assay for predicting the development of post-trauma complications
US20080114576A1 (en) * 2004-12-09 2008-05-15 Matthew Christo Jackson Early Detection of Sepsis
EP1835283A1 (fr) * 2004-12-10 2007-09-19 Sysmex Corporation Procéde support de diagnostic de maladie liée à un dysfonctionnement du système immunitaire et dispositif de sortie d'informations support de diagnostic

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100079292A1 (en) * 1997-01-27 2010-04-01 Lawrence A. Lynn Microprocessor system for the analysis of physiologic and financial datasets
US20070093721A1 (en) * 2001-05-17 2007-04-26 Lynn Lawrence A Microprocessor system for the analysis of physiologic and financial datasets
US10032526B2 (en) 2001-05-17 2018-07-24 Lawrence A. Lynn Patient safety processor
US10297348B2 (en) 2001-05-17 2019-05-21 Lawrence A. Lynn Patient safety processor
US10354753B2 (en) 2001-05-17 2019-07-16 Lawrence A. Lynn Medical failure pattern search engine
US10366790B2 (en) 2001-05-17 2019-07-30 Lawrence A. Lynn Patient safety processor
US9053222B2 (en) 2002-05-17 2015-06-09 Lawrence A. Lynn Patient safety processor
US9953453B2 (en) 2012-11-14 2018-04-24 Lawrence A. Lynn System for converting biologic particle density data into dynamic images
US10354429B2 (en) 2012-11-14 2019-07-16 Lawrence A. Lynn Patient storm tracker and visualization processor
US10540786B2 (en) 2013-02-28 2020-01-21 Lawrence A. Lynn Graphically presenting features of rise or fall perturbations of sequential values of five or more clinical tests

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Publication number Publication date
US11635438B2 (en) 2023-04-25
ES2539854T3 (es) 2015-07-06
WO2011116872A1 (fr) 2011-09-29
CA2788636C (fr) 2020-07-07
HK1177963A1 (zh) 2013-08-30
EP2542894B1 (fr) 2015-04-15
EP2542894A1 (fr) 2013-01-09
JP5828849B2 (ja) 2015-12-09
US20160305957A1 (en) 2016-10-20
CN102782501B (zh) 2015-07-22
CN102782501A (zh) 2012-11-14
JP2013521480A (ja) 2013-06-10
CA2788636A1 (fr) 2011-09-29

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