Anticentromere autoantibodies in patients without Raynaud's disease or systemic sclerosis

Anticentromere autoantibodies (ACA) are associated with Raynaud's disease a nd systemic sclerosis (SSc). ACA usually bind at least one of three major c entromere proteins (CENPs), particularly CENP-B. We identified 16 patients with ACA who do not have Raynaud's disease or SSc. The objective of this st udy was to determine whether these 16 ACA differ in antigenic specificity f rom the ACA found in patients with Raynaud's disease or SSc. Binding of the se serum ACA was tested using competition experiments with recombinant CENP -B, and native centromere proteins from HEp-2 cells and HeLa nuclear extrac ts in ELISAs, immunoblots, and indirect immunofluorescence assays. The ACA from these 16 patients are strikingly different from those obtained from pa tients who have Raynaud's disease or SSc. Only 5 of the 16 index sera (31.2 5%) bound CENP-B from two or more different sources by at least two methods . Six of these 16 sera (37.5%) did not bind CENP-B on ELISA, and 8 of 16 (4 3.75%) did not bind CENP-B on immunoblots. Three sera did not bind CENP-B e ither by ELISA or immunoblots. Of the 13 sera that bound CENP-B, their patt erns of binding to CENP-B strongly suggested that they bind different epito pes within the CENP-B antigen. Independently of their binding to CENP-B, th ese sera reacted mainly with minor CENP antigens detected by HeLa nuclear e xtracts. We have identified unusual ACA not associated with Raynaud's disea se or SSc. (C) 1999 Academic Press.