Centrosome proteins: A major class of autoantigens in scleroderma

Autoantibodies to intracellular antigens are a hallmark of autoimmune disea ses, although their role in disease pathogenesis is unclear. Centrosomes ar e organelles involved in the organization of the mitotic spindle and they a re targets of autoantibodies in systemic sclerosis (SSc). We used recombina nt centrosome autoantigens, centrosome-specific antibodies, and immunoassay s to demonstrate that a significant proportion of SSc patients exhibited ce ntrosome reactivity. Two centrosome proteins cloned in our laboratory were used to screen 129 SSc sera by Western blotting. The same sera were screene d by immunofluorescence using centrosome-specific antibodies to distinguish centrosomes from nuclear speckles commonly stained by SSc sera. Using thes e criteria, 42.6% of SSc patients were autoreactive to centrosomes, a large r percentage than reacted with all other known SSc autoantigens. Most centr osome-positive sera reacted with both centrosome proteins and half were neg ative for other routinely assayed SSe autoantibodies. By these criteria, we have identified a novel class of SSe autoreactivity. Only a small percenta ge of normal individuals and patients with other connective tissue diseases had centrosome reactivity, These results demonstrate that centrosome autoa ntibodies are a major component of autoreactivity in SSc and thus have pote ntial in disease diagnosis. Centrosome autoantigens may be useful in studyi ng the development of autoantibodies and chronic inflammation in SSc and pe rhaps other autoimmune diseases.