The centromere kinesin-like protein, CENP-E. An autoantigen in systemic sclerosis

Autoantibodies directed against centromere proteins (CENPs) are a serologic feature in some patients with systemic sclerosis (SSc). Previous studies have focused on autoantibodies to CENPs A, B, and C. CENP-E is a recently described 312-kd protein that also localizes to the centromere. Therefore, we studied the presence of autoantibodies to recombinant CENP-E in patients with SSc.

Sixty sera from patients with the SSc spectrum of diseases were screened for the presence of autoantibodies against CENP-E, by indirect immunofluorescence and immunoblotting using recombinant CENP-E protein. HLA class II alleles were determined by DNA oligotyping.

Among the SSc sera, 15 of 60 (25%) demonstrated antibody reactivity with recombinant CENP-E, and 14 of these 15 sera (93%) had antibodies directed against another CENP. Anti-CENP-E was seen in 13 of 30 sera with anti-CENP (43%). All patients with anti-CENP-E had a limited form of SSc, known as the CREST variant (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias). When patients with anti-CENPs A, B, or C were compared with patients with anti-CENP-E, no unique clinical features in the anti-CENP-E positive group were identified. Ninety-three percent of the patients with anti-CENP-E had HLA-DQB1 alleles that had polar amino acids at position 26 (primarily DQB1*05), similar to patients with other CENP autoantibodies.

Antibodies to CENP-E are common in patients with SSc, and are seen in higher frequency in sera from patients with a limited form, or CREST variant, of the disease.