Centrosome Proteins: A Major Class of Autoantigens in Scleroderma

Abstract

Autoantibodies to intracellular antigens are a hallmark of autoimmune diseases, although their role in disease pathogenesis is unclear. Centrosomes are organelles involved in the organization of the mitotic spindle and they are targets of autoantibodies in systemic sclerosis (SSc). We used recombinant centrosome autoantigens, centrosome-specific antibodies, and immunoassays to demonstrate that a significant proportion of SSc patients exhibited centrosome reactivity. Two centrosome proteins cloned in our laboratory were used to screen 129 SSc sera by Western blotting. The same sera were screened by immunofluorescence using centrosome-specific antibodies to distinguish centrosomes from nuclear speckles commonly stained by SSc sera. Using these criteria, 42.6% of SSc patients were autoreactive to centrosomes, a larger percentage than reacted with all other known SSc autoantigens. Most centrosome-positive sera reacted with both centrosome proteins and half were negative for other routinely assayed SSc autoantibodies. By these criteria, we have identified a novel class of SSc autoreactivity. Only a small percentage of normal individuals and patients with other connective tissue diseases had centrosome reactivity. These results demonstrate that centrosome autoantibodies are a major component of autoreactivity in SSc and thus have potential in disease diagnosis. Centrosome autoantigens may be useful in studying the development of autoantibodies and chronic inflammation in SSc and perhaps other autoimmune diseases.