Document Detail


Autoantibodies in primary Sjögren's syndrome are directed against proteasomal subunits of the alpha and beta type.
MedLine Citation:
PMID:  10211883     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The proteasome subunit HC9 (alpha3) has recently been identified as a major target of the humoral autoimmune response in patients with autoimmune myositis and systemic lupus erythematosus. Since B cell hyperreactivity is a common feature of systemic autoimmune diseases, patients with primary Sjögren's syndrome (SS) and other control groups were investigated to evaluate the significance of autoantibodies against the proteasome. METHODS: Analyses of autoantibodies directed against the 20S proteasome were performed using enzyme-linked immunosorbent assay, immunoblot, and 2-dimensional electrophoresis. Forty-three patients with primary SS, 47 patients with rheumatoid arthritis including 9 with secondary SS, 19 patients with gastrointestinal tumors, and 80 healthy controls were tested for antiproteasome antibodies. RESULTS: Antiproteasome antibodies were detected in 39% of patients (17 of 43) with primary SS. In contrast, only 1 of 47 patients with rheumatoid arthritis showed positive reactivity (P < 0.001). Serum samples from 19 tumor patients (P < 0.003) and 80 healthy controls (P < 0.001) were serologically negative. Moreover, immunoblotting and 2-dimensional analysis of the antiproteasome response revealed a polyspecific recognition pattern in 7 patients with primary SS. Different proteasomal subunits of the alpha and beta type, including subunits that carried the proteolytic active sites, were recognized by the patients' sera. CONCLUSION: The humoral antiproteasome response in primary SS, in contrast to its secondary form, is characterized by an extensive recognition pattern of several subunits, indicating a polyspecific B cell activation against the 20S proteasome. Moreover, proteolytically active beta-type subunits, which are important for the generation of major histocompatibility complex class I-restricted antigens, appear to be targets of the autoimmune response. The data indicate that the proteasome itself may stand on a cross point of pathways that links mechanisms of the immune defense with features of systemic autoimmunity.
Authors:
E Feist; U Kuckelkorn; T Dörner; H Dönitz; S Scheffler; F Hiepe; P M Kloetzel; G R Burmester
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  42     ISSN:  0004-3591     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  1999 Apr 
Date Detail:
Created Date:  1999-04-30     Completed Date:  1999-04-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  697-702     Citation Subset:  AIM; IM    
Affiliation:
Charité University Hospital, Humboldt University of Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Antinuclear / immunology*
Antibody Specificity*
Cysteine Endopeptidases / analysis,  immunology*
Electrophoresis, Gel, Two-Dimensional
Enzyme-Linked Immunosorbent Assay
Humans
Multienzyme Complexes / analysis,  immunology*
Myositis / enzymology,  immunology
Proteasome Endopeptidase Complex
Sjogren's Syndrome / enzymology,  immunology*
Chemical
Reg. No./Substance:
0/Antibodies, Antinuclear; 0/Multienzyme Complexes; EC 3.4.22.-/Cysteine Endopeptidases; EC 3.4.25.1/Proteasome Endopeptidase Complex

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