EP0538266A1 - PROCEDE DE DETECTION ET DE PREPARATION D'AUTOANTICORPS ANTI-IgE, ET UTILISATION DE CES ANTICORPS COMME AGENTS ACTIFS DANS DES COMPOSITIONS A USAGE THERAPEUTIQUE ET DIAGNOSTIQUE - Google Patents
PROCEDE DE DETECTION ET DE PREPARATION D'AUTOANTICORPS ANTI-IgE, ET UTILISATION DE CES ANTICORPS COMME AGENTS ACTIFS DANS DES COMPOSITIONS A USAGE THERAPEUTIQUE ET DIAGNOSTIQUEInfo
- Publication number
- EP0538266A1 EP0538266A1 EP91909250A EP91909250A EP0538266A1 EP 0538266 A1 EP0538266 A1 EP 0538266A1 EP 91909250 A EP91909250 A EP 91909250A EP 91909250 A EP91909250 A EP 91909250A EP 0538266 A1 EP0538266 A1 EP 0538266A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- ige
- antibodies
- autoantibodies
- recombinant
- carrier
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/42—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins
- C07K16/4283—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an allotypic or isotypic determinant on Ig
- C07K16/4291—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an allotypic or isotypic determinant on Ig against IgE
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/544—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being organic
- G01N33/548—Carbohydrates, e.g. dextran
-
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
-
- 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
- G01N33/6854—Immunoglobulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- 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
Definitions
- the present invention concerns a method for detecting anti-Ige autoantibodies in bodyfluids, a method for preparing auto-anti-IgE antibodies and the use of these antibodies for diagnostic and therapeutic purposes.
- anti-IgE autoantibodies have been described as rheumatoid factors and have been associated with disease ( Magnusson C.G.M., Vaerman J.P., Int.Arch.Allergy appl. Immunol. 79(1986), 149, Stevens W. J., Bridts CH., J.
- Anti-IgE-autoantibodies were first described in 1972 (Williams R.C., Griffith R.W., Emmons J.D., Field R.C., J. Clin. Invest: 51(1972), 955-1003). Later such specific anti-IgE autoantibodies were reported in 1972 (Williams R.C., Griffith R.W., Emmons J.D., Field R.C., J. Clin. Invest: 51(1972), 955-1003). Later such specific anti-IgE autoantibodies were reported in 1972 (Williams R.C., Griffith R.W., Emmons J.D., Field R.C., J. Clin. Invest: 51(1972), 955-1003). Later such specific anti-IgE autoantibodies were reported in 1972 (Williams R.C., Griffith R.W., Emmons J.D., Field R.C., J. Clin. Invest: 51(1972), 955-1003
- anti-IgE autoantibodies failed to trigger histamine release from blood basophils (Nakajima K., de Week A.L., Stadler B.M., Allergy
- the object of the present invention is thus to provide a simple and reliable method for a quantitative detection of anti-IgE-autoantibodies.
- An object of the present invention is also a method for distinction of functional categories of human anti-IgE-autoantibodies for an assessment of their function in allergic and other diseases associated with anti-IgE-autoantibodies.
- Another object of the present invention is a method for the selection of human plasmas comprising anti-IgE-autoantibodies being useful for preparing therapeutic agents against allergic and other IgE
- Another object of the present invention consists in providing a method for purification of anti-IgE autoantibodies having specific properties.
- Another object of the present invention is the in-vivo production of selected anti-IgE-autoantibodies of desired properties by active immunisation by using selected recombinant IgE fragments.
- the present invention comprises the subjects according to the definition in the appended claims.
- auto-anti-IgE antibodies can be detected either in free form or in the form of IgE-IgG complexes. Their fine specifity can be located with the use of recombinant IgE fragments
- Fig. 1a shows the principle of a direct assay for detection of anti-IgE antibodies.
- Fig. 1b shows the principle of a sandwich assay for the detection of IgE/anti-IgE autoantibody immune complexes.
- Fig. 1c shows the principle of a competitive assay for determining the specifity of anti-IgE
- Fig 2. is a diagram corresponding to Table 4 which shows the intradermal reaction of Rh monkey to anti-IgE antibodies.
- Fig. 3 is a diagram corresponding to Table 5 showing the effect of various human sera containing various amounts of anti-IgE antibodies on histamine release induced by Le27 moAb anti-IgE on "stripped" human basophils resensitized by rIgE (CH 1-4).
- Fig. 4 is a diagram showing the effect of various sera containing various amounts of anti-IgE antibodies on Rhesus skin reaction to Le 27 moAb anti-IgE.
- Fig. 5 is a diagram showing the effect of human anti-IgE antibodies (pool) purified by passage on
- immunosorbent columns made of various rlgE (CH 1-4 or CH 3-4) on Le 27 induced skin reaction in Rhesus monkeys.
- Fig. 6 is a diagramm showing the effect of human serum after treatment with mixtures of allergen/IgG anti- allergen (postr.) versus pretreatment serum (pretr,) and serum of a classically desensitized patient on histamine release induced by allergen.
- Fig. 7 is a diagram showing the effect of serum of Rhesus immunized with rlgE (Immun.) versus
- pretreatment serum and serum of Rhesus immunized with allergen on the histamine release induced by
- IgE materials are deposited on the solid phase material, usually in the form of a 1 to 2 ⁇ l dot, at a concentration varying between 100 to 1000 ⁇ g/ml.
- the strip (consisting preferably from PVC coated with
- nitrocellulose is incubated with the serum sample to be investigated at a dilution of 1:1 to 1:10 for a period of 1 - 18 h. After suitable washings, the strip is
- HRP horse radish peroxidase
- monoclonal antibodies against IgG subclasses e.g. IgG1, 2, 3, 4
- immunoglobulin classes e.g. A, M
- This second incubation is usually for a period of 1 to 2 h and is followed by incubation with chromogen.
- the preferred chromogen is a mixture of 2-4 chloronaphtol and hydrogen peroxide.
- the ensuing blue dots may be measured quantitatively by a suitable refractometer.
- the materials dotted are well defined monoclonal anti-IgE antibodies specific for various epitopes on the IgE molecule.
- IgE peptides are first dotted on the solid phase. Following incubation with the serum sample to be investigated for 2 to 18 h and suitable washings, a second incubation occurs with selected HRP-labelled Anti-IgE monoclonal antibodies. If the serum sample comprises IgE antibodies of the same epitope specifity as the HRP labelled anti-IgE antibody, the reaction will be
- auto-anti-IgE antibodies can also be used.
- lymphocytes the killing effect on IgE bearing B
- lymphocytes and the effect on IgE synthesis.
- immunochemical assays provide a rational and efficient basis for different therapeutic approaches and development of corresponding therapeutic products, as illustrated below.
- plasmas obtained by blood donation or plasmapheresis are screened for their content in anti-IgE free or complexed antibodies by the above-described immunochemical tests: According to their content in such antibodies and their specifity, they are pooled and tested also for some functional properties (e.g. histamine release).
- the selected plasmas are then processed for preparing of immunoglobulin fractions by classical techniques in the art (e.g. alcohol fraction or ion exchange chromatography).
- Example 4 Human plasmas obtained by plasmapheresis are submitted to the Immunodot test for detection of anti-IgE antibodies (Table 3) and/or sulfido leukotrienes. The plasmas are also investigated for their capacity to induce histamine release from human basophils (Table 3). The plasmas possessing no, low or high levels of anti- IgE-antibodies and no or high histamine releasing
- anaphylactogenic anti-IgE antibodies will block the effect of anaphylactogenic anti-IgE antibodies (Table 5 and the corresponding Fig. 3 ). A similar inhibiting effect of Ig preparations can be observed on the
- sheep anti-IgE antibodies directed against human IgE have also the property to kill IgE-bearing cells which express the IgE receptor (CD 23).
- some human anti-IgE antibodies possess similar potential in vitro, presumably exerting thereby an inhibiting effect on IgE synthesis in vivo.
- Plasmas containing anti-IgE antibodies selected by the Immunodot test described above are passed over chromatography columns prepared with recombinant IgE-fragments.
- the Ig preparations are then processed according to techniques well known in the art.
- Ig preparations show in functional tests in humans and monkeys (Fig. 5) the desired protective properties, in preventing allergic reactions.
- the preparation of purified auto-anti-IgE antibodies obtained from selected plasmapheresis and passed over appropriate IgE recombinant peptide columns is able to block histamine release from leukocytes of allergic patients challenged by allergen or anti-IgE. It is also capable of blocking the histamine release from leukocytes first "stripped" of their own IgE by acid treatment, reloaded with with recombinant IgE fragment and
- IgG antibodies specific for allergen such as encountered spontaneously in some highly allergic patients or raised by repeated injections of allergen during hyposensitization therapy are
- IgG anti-IgE complexed to allergen-specific IgE and allergen induces in allergic patients the beneficial immunological changes associated with immunotherapy. Since, as seen above, the functional effects of IgG auto anti-IgE may be very different according to their fine specifity, it became imperative to evaluate these therapeutic methods in terms of specific anti-IgE-antibodies.
- Plasmas from hypersensitized patients are selected on the basis of their apparent IgG specifity for allergens (e.g. such as grass pollen), on the basis of allergen-specific IgG tests and analyzed for the presence of auto-anti-IgE antibodies.
- allergens e.g. such as grass pollen
- Plasma pools rich or devoid of auto-anti-IgE antibodies are used as source of immunoglobulin
- This technique can in principle be used also for fostering other immune responses which may rest upon IgE activities, such as the immune defense against some parasites.
- the presence of blocking antibodies for IgE has been for example described in filiarosis.
- IgE-vaccine recombinant fragments, in order to raise beneficial anti- IgE antibodies in allergic patients
- Anti-IgE antibodies of the desired specifity having the desired blocking anti-allergic activity can be produced actively.
- Example 7 Recombinant IgE peptides of various sizes and encompassing various domains of the IgE heavy chain are produced according to combinations of procedures known in the art.
- the antibodies raised have the functional properties required, based on the previous analysis of similar but naturally occurring human auto- anti-IgE antibodies. In particular, these antibodies are able to recognize IgE and IgE fragments. These antibodies have also the capacity to block histamine release induced by anaphylactogenic anti-IgE monoclonal antibodies or allergen (Fig. 7).
- Table 7 Schedule and amounts of allergen and antibody to be used as complexes for hyposensitization therapy
- allergen-specific "IgG antibodies” which contain as well antiallergen IgE complexed with IgG anti-IgE autoantibodies.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Microbiology (AREA)
- Pathology (AREA)
- Food Science & Technology (AREA)
- Biotechnology (AREA)
- General Physics & Mathematics (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Rehabilitation Therapy (AREA)
- Rheumatology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
Abstract
Selon un procédé de détection d'autoanticorps libres ou complexes dirigés contre l'IgE, des échantillons, en particulier de sang humain, sont mis en contact et incubés avec du matériau contenant de l'IgE sous la forme d'anticorps d'IgE, de peptides d'IgE ou de fragments d'IgE recombinés fixés sur un véhicule solide. Le procédé peut être effectué sous forme d'un dosage direct, d'un dosage en sandwich ou d'un dosage compétitif. Le procédé peut être utilisé pour préparer des anticorps humains antiallergiques dirigés contre l'IgE et faisant preuve d'une activité de blocage thérapeutique en ce qui concerne les affections allergiques. Selon ce procédé, un fluide corporel humain contenant des autoanticorps anti-IgE est choisi selon le processus décrit ci-dessus, et l'immunoglobuline contenue dans le fluide est concentrée, de préférence par fractionnement à l'alcool ou par chromatographie par échange d'ions. Afin d'obtenir des autoanticorps anti-IgE purs, l'on isole ceux-ci à partir du produit concentré par chromatographie par affinité. Les anticorps anti-IgE et des complexes de ceux-ci sont utilisés comme principes actifs dans des compositions pharmaceutiques destinées au traitement d'affections allergiques. La formation d'autoanticorps anti-IgE peut être induite in vivo par des peptides d'IgE ou des fragments d'IgE recombinés.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002086605A CA2086605A1 (fr) | 1991-05-10 | 1991-05-10 | Methodes de detection et de preparation des auto-anticorps anti-ige et utilisation de ces anticorps comme agents actifs dans des compositions diagnostiques et therapeutiques |
PCT/EP1991/000881 WO1992021031A1 (fr) | 1991-05-10 | 1991-05-10 | PROCEDE DE DETECTION ET DE PREPARATION D'AUTOANTICORPS ANTI-IgE, ET UTILISATION DE CES ANTICORPS COMME AGENTS ACTIFS DANS DES COMPOSITIONS A USAGE THERAPEUTIQUE ET DIAGNOSTIQUE |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0538266A1 true EP0538266A1 (fr) | 1993-04-28 |
Family
ID=4150928
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP91909250A Withdrawn EP0538266A1 (fr) | 1991-05-10 | 1991-05-10 | PROCEDE DE DETECTION ET DE PREPARATION D'AUTOANTICORPS ANTI-IgE, ET UTILISATION DE CES ANTICORPS COMME AGENTS ACTIFS DANS DES COMPOSITIONS A USAGE THERAPEUTIQUE ET DIAGNOSTIQUE |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP0538266A1 (fr) |
JP (1) | JPH05508220A (fr) |
CA (1) | CA2086605A1 (fr) |
WO (1) | WO1992021031A1 (fr) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19505266C1 (de) * | 1995-02-16 | 1996-10-02 | Brahms Diagnostica Gmbh | Verwendung von polyklonalen humanen anti-hTg-Autoantikörpern als Reagenz für die klinische Diagnostik von Schilddrüsen-Autoimmunerkrankungen sowie Reagenziensatz für eine Bestimmung von anti-hTg-Autoantikörpern in Patientenseren |
EP1671646A3 (fr) * | 1998-09-18 | 2007-08-29 | Dynavax Technologies Corporation | Procédés de traitement de troubles associés à IgE et compositions pouvant être utilisées à cet effet. |
EP1113818B1 (fr) * | 1998-09-18 | 2006-05-17 | Dynavax Technologies Corporation | PROCEDES DE TRAITEMENT DE TROUBLES ASSOCIES A IgE ET COMPOSITIONS POUVANT ETRE UTILISEES A CET EFFET |
US6787524B2 (en) | 2000-09-22 | 2004-09-07 | Tanox, Inc. | CpG oligonucleotides and related compounds for enhancing ADCC induced by anti-IgE antibodies |
CA2556557A1 (fr) * | 2004-02-26 | 2005-09-09 | Alk Abello A/S | Procede pour evaluer le potentiel therapeutique d'un vaccin a administration mucosale |
CN101223448B (zh) * | 2005-05-20 | 2012-01-18 | 健泰科生物技术公司 | 来自自身免疫病受试者的生物学样品的预处理 |
AR065921A1 (es) * | 2007-04-02 | 2009-07-08 | Amgen Fremont Inc | Anticuerpos anti-ige |
JP5504945B2 (ja) * | 2010-02-12 | 2014-05-28 | 日東紡績株式会社 | Ftcdとその自己抗体との複合体の免疫測定方法、それに用いるキット及びそれを用いた癌判定方法 |
CN113583134B (zh) * | 2020-04-30 | 2024-06-04 | 天辰生物医药(苏州)有限公司 | 分离的抗原结合蛋白及其用途 |
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1991
- 1991-05-10 CA CA002086605A patent/CA2086605A1/fr not_active Abandoned
- 1991-05-10 WO PCT/EP1991/000881 patent/WO1992021031A1/fr not_active Application Discontinuation
- 1991-05-10 JP JP91508475A patent/JPH05508220A/ja active Pending
- 1991-05-10 EP EP91909250A patent/EP0538266A1/fr not_active Withdrawn
Non-Patent Citations (1)
Title |
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See references of WO9221031A1 * |
Also Published As
Publication number | Publication date |
---|---|
JPH05508220A (ja) | 1993-11-18 |
CA2086605A1 (fr) | 1992-11-11 |
WO1992021031A1 (fr) | 1992-11-26 |
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