Autoantibodies to the 27 C-terminal amino acids of calpastatin are detected in a restricted set of connective tissue diseases and may be useful for diagnosis of rheumatoid arthritis in community cases of very early arthritis

Background. Calpastatin is the natural inhibitor of calpains, a protease th at is overexpressed in rheumatoid synovial tissue and plays a key role in c artilage destruction. Autoantibodies to calpastatin (ACAST) were recently d etected in rheumatoid arthritis (RA). Our aim was to determine their preval ence and their clinical significance. Methods. ACAST were detected in a solid-phase enzyme-linked immunosorbent a ssay (ELISA) using a synthetic peptide corresponding to the 27 C-terminal a mino acids of calpastatin (CAST-C27) as the antigen. All sera reacting with this peptide also bound to purified erythrocyte calpastatin in an ELISA an d/or an immunoblot assay. The frequencies and clinical significance of ACAS T-C27 were assessed in sera from a well-documented population of 102 commun ity-recruited patients (76 females; mean age 50 yr) with RA that had been e volving for <5 yr (median 2 yr) (group 1), 109 healthy blood donors, 289 pa tients with non-RA rheumatic disease and 88 community cases of very early ( median 4 months) arthritis, i.e. 58 RA and 30 non-RA patients (group 2). Results. The sensitivity of ACAST-C27 for RA was 19.5% (20/102) in group 1 and 10.3% (6/58) in group 2, These antibodies were also found in patients w ith anti-double-stranded DNA-positive systemic lupus erythematosus (SLE) (1 5.5%) and patients with anti-Ro-positive Sjogren's syndrome (18.5%). Howeve r, they were not detected in cases of rheumatism resembling early RA, i.e. peripheral spondylarthropathies. ACAST-C27 were not detected in the 30 non- RA patients of group 2. They were predominantly of immunoglobulin isotype G 3 and exclusively expressed <lambda> chains. Among ACAST-C27-positive sera, eight out of 20 (group 1) and four out of six (group 2) were negative for rheumatoid factor and anti-keratin antibodies/antiperinuclear factor. No re lationship was found between ACAST-C27 and clinical, biological or radiolog ical findings. Conclusion. ACAST-C27 are detected only in, a restricted set of connective tissue diseases and therefore appear to be specific for RA when antibodies that are usually associated with SLE or primary Sjogren's syndrome are nega tive. Because of their presence in community cases of very early RA, partic ularly in some seronegative forms, ACAST-C27 may be useful in discriminatin g recent-onset RA from the more common non-RA rheumatic diseases, such as s pondylarthropathies.