Abstract
STATEMENT OF FINDINGS: An inception cohort of 238 patients having peripheral joint synovitis of less than 12 months duration was evaluated clinically and followed prospectively for 1 year to determine the clinical significance of a number of rheumatoid arthritis (RA) associated autoantibodies. Serum samples collected at the time of the initial evaluation were tested for rheumatoid factor (RF) and antibodies to Sa (anti-Sa), RA-33, (pro)filaggrin [antifilaggrin antibody (AFA)], cyclic citrullinated peptide (anti-CCP), calpastatin, and keratin [antikeratin antibody (AKA)]. RF had a sensitivity of 66% and a specificity of 87% for RA. Anti-Sa, AFA, and anti-CCP all had a specificity of more than 90%, but a sensitivity of less than 50% for this diagnosis. Overall, there was a high degree of correlation between AFA, AKA, anti-Sa or anti-CCP, this being highest between anti-Sa and anti-CCP (odds ratio, 13.3; P < 0.001). Of the 101 patients who were positive for at least one of these four autoantibodies, 57% were positive for only one. Finally, anti-SA identified a subset of predominantly male RA patients with severe, erosive disease. Anti-SA, AFA and anti-CCP are all specific for early RA but, overall, have little additional diagnostic value over RF alone. Although these antibodies may preferentially recognize citrullinated antigens, the modest degree of concordance between them in individual patient sera suggests that it is unlikely a single antigen is involved in generating these responses.
Highlights
A spectrum of autoantibodies is known to be associated with rheumatoid arthritis (RA)
Of the 238 patients with synovitis of recent onset in the cohort, 106 (45%) met RA criteria, 102 (96%) of whom met the criteria on their initial visit
Despite a well-documented lack of specificity, rheumatoid factor (RF) continues to be a central part of the definition of RA, primarily because of its favorable sensitivity profile
Summary
A spectrum of autoantibodies is known to be associated with RA. There continues to be uncertainty as to what stage of the disease each of these autoantibodies develop, and whether they are associated with unique clinical features. There was a high degree of correlation between AFA, AKA, anti-Sa or anti-CCP, this being highest between anti-Sa and anti-CCP (odds ratio, 13.3; P < 0.001) Despite this high level of correlation, of the 101 patients who were positive for at least one of these four autoantibodies, 57% were positive for only one, suggesting considerable variability in individual reactivity patterns. AKA, APF , AFA, and anti-Sa have all been shown to be associated with RA, and appear to be more specific than RF for this disease [1,2,3,4,5,6,7,8,9]. AKA, APF, and AFA identify epitopes carried by keratin, profilaggrin and filaggrin, respectively [3,6,14,15] These proteins follow a common post-translational pathway, which involves a peptidyl-arginine to citrulline deimination. Anti-RA-1 antibodies are directed towards domains 3 and 4 of calpastatin, the natural inhibitor of calpains, which are members of the cysteine proteinases that have been implicated in articular damage [13]
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