THE CONCURRENCE OF RHEUMATOID-ARTHRITIS AND LIMITED SYSTEMIC-SCLEROSIS - CLINICAL AND SEROLOGIC CHARACTERISTICS OF AN OVERLAP SYNDROME

Objective, The characteristics of 3 patients with longstanding rheumat oid arthritis (RA) and consecutive evolution of limited cutaneous syst emic sclerosis (IcSSc) were evaluated and compared with those of patie nts with IcSSc alone (n = 20) or with RA alone (n 120), Methods, Clini cal features of the different patient populations were compared. Serol ogic analyses included tests for antinuclear antibodies (ANA) and ANA subsets, in particular anticentromere antibodies (ACA) and anti-hetero geneous nuclear RNP (hnRNP)-A2/RA33 (anti-A2/RA33), Results. The 3 pat ients with RA developed IcSSc 11, 29, or 50 years after the onset of R A. Features of IcSSc were Raynaud's phenomenon, sclerodactyly, and tel angiactasias in all 3 patients, and esophageal dysmotility in I patien t. Rheumatoid factor (RF) and anti-A2/ RA33 were each found in 2 patie nts, and 1 of these patients was seropositive for both RF and anti-A2/ RA33. ACA titers were positive in all cases, However, similar to the d evelopment of RA prior to IcSSc, the occurrence of autoantibodies typi cal of RA preceded the occurrence of ACA, at least in 2 of the patient s. Using affinity-purified antibodies, cross-reactivities between anti -centromere protein A (CENP-A) and anti-CENP-B antibodies with anti-A2 /RA33 antigens were seen in the 2 anti-A2/RA33-positive patients. Such cross-reactivities were not found in IcSSc patients without concomita nt RA. Epitope mapping revealed that both autoantibody specificities r ecognized the known major epitopes: anti-CENP-B reacted with the C-ter minal region and anti-A2/RA33 with the second RNA binding domain in th e N-terminal region of hnRNP-A2. Conclusion. The RA-lcSSc overlap synd rome in these 3 patients with longstanding RA was characterized by an incomplete CREST (calcinosis, Raynaud's phenomenon, esophageal dysmoti lity, sclerodactyly, and telangiectasias) syndrome. The study demonstr ated the presence of autoantibodies typical of both diseases and cross -reactivity of ACA,vith hnRNP-A2/RA33 in the sera of these patients.