title: Comparison of IgA-alpha1-antitrypsin levels in rheumatoid arthritis and seronegative oligoarthritis: complex formation is not associated with inflammation per se.
abstract: Serum complexes between IgA and alpha1-antitrypsin (IgA alpha1AT) have been found at raised levels in early rheumatoid arthritis (RA), where they appear to be associated with more erosive disease. We have now measured the levels of these complexes in the sera and synovial fluid of patients with RA and seronegative oligoarthritis to determine whether there is a relationship between complex levels and joint inflammation, and if bacterial stimulation of the mucosa is associated with complex formation in seronegative oligoarthritis. IgA-alpha1AT complexes were measured in patients with RA (n = 75) and seronegative oligoarthritis, with or without definite reactive arthritis (n = 28), using a newly developed sandwich ELISA. The results were compared with serum levels from healthy volunteers (n = 30). IgA and alpha1AT were also measured using ELISA and radial immunodiffusion (RID) techniques, respectively. IgA-alpha1AT complex levels in the sera of RA patients [mean = 25.6 arbitrary units (au)] were significantly higher (P = 0.0034) than those in patients with seronegative oligoarthritis (mean = 12.36 au) and healthy controls (mean = 8.08 au). There was no evidence for the inflamed joint being the source of IgA-alpha1AT complexes since synovial fluid levels were lower than corresponding serum levels, although higher amounts were found in RA than seronegative oligoarthritis (12.84 au vs 4.11 au, P = 0.01). Serum levels of IgA and alpha1AT were similar in RA and seronegative oligoarthritis patients, and were higher than in normals. There was a significant correlation between complex and serum IgA levels in RA (r = 0.49, P < 0.001) and seronegative oligoarthritis (r = 0.53, P < 0.001) patients, although no relationship was found with alpha1AT levels. There was no correlation with other markers of the acute-phase response (C-reactive protein, erythrocyte sedimentation rate), nor with any clinical markers. In RA patients, serum complex levels were significantly higher in seropositive than seronegative patients (30.75 vs 16.48 au, P = 0.03), and we have demonstrated that a small amount of alpha1AT may be complexed with IgA rheumatoid factor. Our data suggest that the formation of IgA-alpha1AT complexes is not associated with inflammation per se, and does not appear to be related to bacterial stimulation of the mucosal immune system in patients with seronegative oligoarthritis.
authors.affiliation: Staffordshire Rheumatology Centre/Keele University, Stoke-on-Trent.
authors.forename: L J
authors.initials: LJ
authors.lastname: Scott
authors.forename: E L
authors.initials: EL
authors.lastname: Evans
authors.forename: P T
authors.initials: PT
authors.lastname: Dawes
authors.forename: G I
authors.initials: GI
authors.lastname: Russell
authors.forename: D L
authors.initials: DL
authors.lastname: Mattey
mesh_terms: D000328:Adult; D000936:Antigen-Antibody Complex / Q000032:analysis / Q000097:blood*; D016918:Arthritis, Reactive / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood*; D007596:Joints / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000737:chemistry / Q000276:immunology; D000515:alpha 1-Antitrypsin / Q000032:analysis / Q000276:immunology* / Q000378:metabolism
chemical_list: D000936:Antigen-Antibody Complex; D007070:Immunoglobulin A; D000515:alpha 1-Antitrypsin