The clinical expression in anticentromere antibody-positive patients is not specified by the epitope recognition of CENP-B antigen.
Centromere protein B (CENP-B), which is an alphoid DNA binding protein, is the target antigen in autoimmune disease patients (often with scleroderma). From our previous analysis of the reactivity of anticentromere sera, four independent epitopes were identified on recombinant CENP-B. The anticentromere sera displayed heterogeneity in their patterns of reactivity to the four epitopes. We have investigated to what extent this heterogeneity of the target autoepitope on CENP-B accounts for the clinical diversity of anticentromere antibody (ACA)-positive patients. A major autoepitope, epitope I, was recognized by all 40 ACA-positive sera; however, the other three epitopes were recognized differently from case to case. We could not find any significant correlation between the reactivity to CENP-B autoepitopes and the clinical presentation of ACA-positive patients. There was considerable clinical diversity, even among the nine patients showing specificity for the single major autoepitope. In conclusion, we found that, although ACA-positive patients were both clinically and immunologically heterogeneous, in most respects the clinical expression appeared to be independent of the reactivity to the CENP-B autoepitope, a finding which suggests that identification of the target epitope of CENP-B is unlikely to assist in the clinical classification of the disease in ACA-positive patients. The identification of multiple B cell epitopes on CENP-B is consistent with the concept that the self-antigen drives the antibody response. However, factors other than CENP-B autoepitope specificity must determine the clinical expression of ACA responses.
D000328:Adult; D001324:Autoantigens / Q000097:blood / Q000276:immunology*; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology*; D051936:Centromere Protein B; D002868:Chromosomal Proteins, Non-Histone / Q000097:blood / Q000276:immunology*; D004268:DNA-Binding Proteins; D000939:Epitopes / Q000097:blood / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007518:Isoantibodies / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged
D001324:Autoantigens; C497926:CENPB protein, human; D051936:Centromere Protein B; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000939:Epitopes; D007136:Immunoglobulins; D007518:Isoantibodies; C051138:anti-c antibody