title: Functional autoantibodies against serpin E2 in rheumatoid arthritis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University Hospital, University of Zurich, Zurich, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Maciejewska-Rodrigues
authors.forename: M
authors.initials: M
authors.lastname: Al-Shamisi
authors.forename: H
authors.initials: H
authors.lastname: Hemmatazad
authors.forename: C
authors.initials: C
authors.lastname: Ospelt
authors.forename: M C
authors.initials: MC
authors.lastname: Bouton
authors.forename: D
authors.initials: D
authors.lastname: Jäger
authors.forename: A P
authors.initials: AP
authors.lastname: Cope
authors.forename: P
authors.initials: P
authors.lastname: Charles
authors.forename: D
authors.initials: D
authors.lastname: Plant
authors.forename: J H W
authors.initials: JH
authors.lastname: Distler
authors.forename: R E
authors.initials: RE
authors.lastname: Gay
authors.forename: B A
authors.initials: BA
authors.lastname: Michel
authors.forename: A
authors.initials: A
authors.lastname: Knuth
authors.forename: M
authors.initials: M
authors.lastname: Neidhart
authors.forename: S
authors.initials: S
authors.lastname: Gay
authors.forename: A
authors.initials: A
authors.lastname: Jüngel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015535:Arthritis, Psoriatic / Q000097:blood / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000097:blood / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D015843:Serpins / Q000276:immunology*; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000276:immunology; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D011994:Recombinant Proteins; D015843:Serpins; D014568:Urokinase-Type Plasminogen Activator