Document Detail

Functional autoantibodies against serpin E2 in rheumatoid arthritis.
MedLine Citation:
PMID:  20039430     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To search for novel autoantibodies in patients with rheumatoid arthritis (RA) in an effort to better understand the processes of joint destruction in this disease. METHODS: Using a modified SEREX technique and complementary DNA derived from RA synovium, serpin E2 was identified as a novel autoantigen and was analyzed by immunohistochemistry. Levels of anti-serpin E2 autoantibodies in serum and synovial fluid from patients with RA, osteoarthritis (OA), psoriatic arthritis, and ankylosing spondylitis, and/or from healthy individuals were assessed by enzyme-linked immunosorbent assay. Since serpin E2 is an inhibitor of serine proteases, we studied the inhibitory activity of serpin E2 toward its target, urokinase plasminogen activator (uPA), in vitro in the presence of isolated anti-serpin E2 autoantibodies and in vivo using the uPA activity assay. RESULTS: We identified autoantibodies against serpin E2 by the SEREX technique. Serpin E2 was overexpressed in RA synovial tissues as compared with OA synovial tissues. Significantly higher levels of anti-serpin E2 autoantibodies were present in samples of synovial fluid (28%) and serum (22%) from RA patients as compared with OA patients (0 and 6%, respectively) or with healthy individuals (6% of sera). Most importantly, anti-serpin E2 autoantibodies isolated from RA sera reversed the inhibitory activity of serpin E2 by 70%. Furthermore, the levels of anti-serpin E2 autoantibodies correlated with the uPA activity in vivo. CONCLUSION: This study characterizes a functional property of a novel autoantibody in RA. Since anti-serpin E2 autoantibodies interfere with the inhibitory activity of serpin E2 toward serine proteases, they might facilitate the joint destruction in RA.
H Maciejewska-Rodrigues; M Al-Shamisi; H Hemmatazad; C Ospelt; M C Bouton; D J?ger; A P Cope; P Charles; D Plant; J H W Distler; R E Gay; B A Michel; A Knuth; M Neidhart; S Gay; A J?ngel
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  62     ISSN:  0004-3591     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-13     Completed Date:  2010-03-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  93-104     Citation Subset:  AIM; IM    
University Hospital, University of Zurich, Zurich, Switzerland.
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MeSH Terms
Aged, 80 and over
Arthritis, Psoriatic / blood,  immunology
Arthritis, Rheumatoid / blood,  immunology*
Autoantibodies / blood*
Enzyme-Linked Immunosorbent Assay
Gene Expression Profiling
Middle Aged
Oligonucleotide Array Sequence Analysis
Osteoarthritis / blood,  immunology
Recombinant Proteins / immunology
Serpins / immunology*
Spondylitis, Ankylosing / blood,  immunology
Synovial Fluid / immunology,  metabolism
Synovial Membrane / metabolism,  pathology
Urokinase-Type Plasminogen Activator / antagonists & inhibitors
Young Adult
Reg. No./Substance:
0/Autoantibodies; 0/Recombinant Proteins; 0/Serpins; EC Plasminogen Activator

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