CENP-O, a Protein Localized at the Centromere Throughout the Cell Cycle, Is a Novel Target Antigen in Systemic Sclerosis

Objective. CENP-A, -B, and -C are major centromere components and the main targets of anticentromere antibodies (ACA). Many other proteins are also assembled around CENP-A nucleosomes in interphase nuclei to form the interphase centromere complex (ICEN). The CENP-O protein is a component of the ICEN that localizes at the centromere throughout the cell cycle. We investigated whether CENP-O is also targeted by sera from patients with systemic autoimmune diseases. Methods. Sera from 114 patients with ACA and 142 patients without ACA were analyzed. Western blotting and an ELISA with bacterially expressed recombinant CENP-O protein were performed to screen for the presence of anti-CENP-O antibodies. In addition, anti-CENP-O antibody-positive sera were tested by Western blotting HeLa cell extracts to examine reactivity with the major centromere antigens. Results. Four female patients with ACA had anti-CENP-O antibodies. There was no correlation of anti-CENP-O antibodies with specific clinical features or other serological features. However, one of the 4 patients, who showed a unique clinical course of scleroderma, had sera with markedly high reactivity to CENP-O. Conclusion. CENP-O protein is a novel centromere antigen that is recognized by a very minor population of ACA-positive patients with scleroderma. Because CENP-O is all ICEN component, ICEN may be a large antigenic structure in systemic autoimmunity. (First Release March 15 2009; J Rheumatol 2009;36:781-6; doi: 10.3899/jrheum.080726)