Abstract
Joint-specific self-Ags are considered to play an important role in the induction of synovial T and B cell expansion in human rheumatoid arthritis (RA). However, the nature of these autoantigens is still enigmatic. In this study a somatically mutated IgG2 lambda B cell hybridoma was established from the synovial membrane of an RA patient and analyzed for its Ag specificity. A heptameric peptide of cartilage oligomeric matrix protein (COMP) could be characterized as the target structure recognized by the human synovial B cell hybridoma. The clonotypic V(H) sequences of the COMP-specific hybridoma could also be detected in synovectomy material derived from five different RA patients but in none of the investigated osteoarthritis cases (n = 5), indicating a preferential usage of V(H) genes closely related to those coding for a COMP-specific Ag receptor in RA synovial B cells. Moreover, the COMP heptamer was preferentially recognized by circulating IgG in RA (n = 22) compared with osteoarthritis patients (n = 24) or age-matched healthy controls (n = 20; both p < 0.0001). Hence, the COMP-specific serum IgG is likely to reflect local immune responses toward a cartilage- and tendon-restricted Ag that might be crucial to the induction of tissue damage in RA.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Monoclonal* / biosynthesis
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Antibodies, Monoclonal* / blood
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Antibodies, Monoclonal* / genetics
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Antibodies, Monoclonal* / metabolism
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Antibody Specificity* / genetics
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Arthritis, Rheumatoid / blood
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Arthritis, Rheumatoid / immunology*
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Arthritis, Rheumatoid / pathology
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Autoantibodies / blood
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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B-Lymphocytes / pathology
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Binding Sites, Antibody
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Cartilage Oligomeric Matrix Protein
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Cartilage, Articular / immunology*
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Epitopes, B-Lymphocyte / immunology*
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Epitopes, B-Lymphocyte / isolation & purification
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Extracellular Matrix Proteins / immunology*
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Extracellular Matrix Proteins / metabolism
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Gene Expression Regulation / immunology
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Glycoproteins / immunology*
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Glycoproteins / metabolism
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Humans
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Hyalin / immunology
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Hybridomas / immunology*
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Hybridomas / metabolism
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Hybridomas / pathology
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Immunoblotting
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Immunoglobulin G / blood
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Immunoglobulin Heavy Chains / biosynthesis
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Immunoglobulin Heavy Chains / genetics
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Matrilin Proteins
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Osteoarthritis / blood
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Osteoarthritis / immunology
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Osteoarthritis / pathology
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Peptide Fragments / immunology
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Peptide Fragments / isolation & purification
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Synovial Membrane / immunology*
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Synovial Membrane / metabolism
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Synovial Membrane / pathology
Substances
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Antibodies, Monoclonal
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Autoantibodies
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Cartilage Oligomeric Matrix Protein
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Epitopes, B-Lymphocyte
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Extracellular Matrix Proteins
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Glycoproteins
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Immunoglobulin G
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Immunoglobulin Heavy Chains
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Matrilin Proteins
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Peptide Fragments
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TSP5 protein, human