Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1997-05-08
1999-11-02
Eisenschenk, Frank C.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
436506, 436509, 5303891, 530350, G01N 3353, G01N 33564
Patent
active
059768100
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a method of immunologically-detecting rheumatism and a reagent of immunologically detecting therefor. In more detail, it relates to a method of immunologically detecting antibodies which react with autoantigenic proteins present in the serum of a rheumatic patient and a reagent therefor.
2. Description of the Prior Art
Rheumatism is a chronic systemic inflammatory autoimmune disease that causes swelling and pain in the multi-joints and malaise, infirmity, weight loss, febricula and anorexia in other body organs. Criteria for the classification of rheumatism established by American Rheumatoid Association have been currently used in clinical diagnoses (Arnet, F. C. et al. Arthritis Rheum. vol. 305, Abstract 45, 1987); (1) morning stiffness, (2) arthritis of 3 or more joint areas, (3) arthritis of hand joints, (4) symmetric arthritis, (5) radiographic changes, (6) serum rheumatoid factor, (7) rheumatoid nodules. For the classification purposes, a patient shall be diagnosed to have rheumatism if he/she has satisfied at lease 4 of these 7 criteria. Moreover, by examining blood, there are chronic inflammatory symptoms such as acceleration of erythrocyte sedimentation rate and increase of C-reative protein reaction in the sera. There are also special symptoms such as anemia, increase of white blood cells, increase of thrombocytes, increase of .gamma.-globulin in sera. However, all the diagnosis are applied to patients after the occurrence of some symptoms. Therefore, it has long been desired that a new method should be established enabling to diagnose patients before the occurrence of the clinical symptoms or with early staged symptoms. The present invention attempts to find an early diagnosis of rheumatism before the obvious occurrence of the symptoms. This invention relates to a method of detecting a serum based on rheumatic specific antigens at the early stage and it is considered highly useful for its convenience and reliability.
DETAILED DESCRIPTION OF THE INVENTION
From the point of view that rheumatism is an autoimmune disease and that focusing at autoantibodies present in the serum of a rheumatic patient, the present invention attempts to detect autoantibodies which reacts with specific autoantigens. The inventors of the present invention found that ezrin, radixin and moesin were antigen substances which reacted with the autoantibodies present in the serum of a rheumatic patient, which led to the completion of the invention.
Therefore, the present invention provides for a method of detecting autoantibodies present in the serum of a rheumatic patient by reacting one or more proteins selected from the group consisting of ezrin, radixin and moesin of mammalian origin and/or one or more peptides comprising at least 9 or more consecutive amino acid residues in an amino acid sequence derived from ezrin, radixin and moesin with human sera. Although ezrin, radixin, moesin which are derived from mammalian origin are applicable, those derived from human are specially more preferable.
Autoantigen substances containing one or more than two various kinds can be used for the detection.
The present invention provides for a method of detecting autoantibodies present in the serum of a rheumatic patient by reacting radixin with human sera, a method of detecting autoantibodies present in the serum of a rheumatic patient by reacting radixin and moesin with human sera, and a method of detecting autoantibodies present in the serum of a rheumatic patient by reacting ezrin, radixin and moesin with human sera.
Further, the present invention relates to a reagent for immunologically detecting rheumatism containing as an antigen at least one mammalian protein selected from the group of ezrin, radixin and moesin and/or a peptide composed of at least nine consecutive amino acid residues
Further, the present invention provides for a reagent for immunologically detecting rheumatism containing radixin as an antigen, a reagent for immunologically detecting
REFERENCES:
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Kathleen L. Gould et al., "cDNA Cloning and Sequencing of the Protein-Tyrosine Kinase Substrate, Ezrin, Reveals Homology to Band 4.1" The EMBO Journal, vol. 8, No. 13, pp. 4133-4142 (1989).
Sachiko Tsukita et al., "A New 82-kD Barbed End-capping Protein (Radixin) Localized in the Cell-to-Cell Adherens Junction: Purification and Characterization," J. Cell Biol., vol. 108, pp. 2369-2382 (19890.
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Naruki Sato et al., "A Gene Family Consisting of Ezrin, Radixin and Moesin--Its Specific Localization at Actin Filament/plasma Membrane Association Sites," J. Cell Sci., vol. 103, pp. 131-143 (1992).
Mark Egerton et al., "Identification of Ezrin as an 81-kDa Tyrosine-Phosphorylated Protein in T Cells," J. Immunol., vol. 149, pp. 1847-1852 (1992).
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Kimrua Michio
Takeuchi Fujio
Wagatsuma Masako
Watanabe Hiroshi
Eisenschenk Frank C.
Hoechst Pharmaceuticals & Chemicals K.K.
Rabin Evelyn
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