Circulating anticentromere CENP-A and CENP-B antibodies in patients with diffuse and limited systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis

Objective, To determine the disease sensitivity and specificity of testing for autoantibodies against 2 of the 3 main human centromere antigenic compo nents. CENP-A and CENP-B (recombinant, expressed in baculovirus). Methods. ELISA with CENP-A and CENP-B antigens were used to rest 45 sera sh owing a centromere pattern by immunofluorescence (IFA) and sera from 96 pat ients with systemic sclerosis (SSc), subdivided into diffuse (dSSc) and lim ited (lSSc) forms. For controls, the same tests were performed on sera from 100 patients with rheumatoid arthritis (RA), 100 with systemic lupus eryth ematosus (SLE), and 50 random blood donors. Sera from all the patients with SSc were also tested for the presence of anti-Scl70 antibody by ELISA (bov ine antigen), and for pattern and titer by IFA (HEp-2 cells). Results. Of the 45 IFA positive sera, 93% were positive for anti-CENP-A and 91% for anti-CENP-B. There was a very good quantitative correlation betwee n the antibody levels against these 2 centromere components (r = 0.597; p < 0.001). Anti-CENP-A and B were found in 48% of patients with lSSc, and in 11% and 9%, respectively, of those with dSSc. The difference in the frequen cy of anti-CENP-A between the 2 patient groups was significant (chi-squared , p < 0.001). Similar levels of anticentromere staining pattern by IFA were observed for these 2 groups. Anti-Scl70 was elevated in 8% of lSSc and 25% of dSSc patients; this difference was also significant (chi-squared, p = 0 .02). Neither CENP-A nor CENP-B reacted with IgG from SSc patients containi ng anti-Scl70. The frequency of abnormal levels in patients with SLE and RA was, respectively, 11% and 3% for anti-CENP-A and 4% and 3% for anti-CENP- B. The reaction of IgG from SLE and RA patients with CENP-A was not inhibit ed by histone H3, i.e., it was not due to recognition of the histone-like d omain in CENP-A. Thus, when 96 SSc patients were compared to 200 patients w ith RA and SLE, the disease specificity of anti-CENP-A and B was 93% and 96 .5%, respectively. Conclusion. In addition to IFA, ELISA tests for CENP-A and CENP-B yield res ults with similar sensitivity and specificity for the diagnosis of SSc. CEN P-A and CENP-B are primarily associated with lSSc. In SSc the autoantibody response is directed simultaneously and with similar amplitude against thes e 2 components of the centromere structure, whereas in other autoimmune dis eases the response is directed mainly against one of the 2 components.