AUTOANTIBODIES TO A GROUP OF CENTROSOMAL PROTEINS IN HUMAN AUTOIMMUNESERA REACTIVE WITH THE CENTROSOME

Objective. Human autoantibodies reacting with protein components of th e microtubule organizing center of the cell, the centrosome, are rare and have not been extensively studied, We therefore investigated the n umber, type, and frequency of autoantibodies reactive with centrosomal proteins in a cohort of human sera. Methods. To establish the type of autoantibodies found in autoimmune sera reactive with the centrosome, we used a prototype human serum, which was chosen for its intense rea ctivity with the centrosome throughout the cell cycle, to screen a HeL a complementary DNA (cDNA) (expression) library, Positive cDNA clones were sequenced and classified as encoding either known centrosomal aut oantigens, known centrosomal proteins but unknown as human autoantigen s, or previously unknown centrosomal antigens, To investigate whether these centrosomal autoantibody classes were characteristic of centroso mal-reactive sera, sera from 21 subjects with centrosomal reactivity b y indirect immunofluorescence were characterized by Western blotting f or reactivity to recombinant protein from each of the classes of centr osomal antigens, Clinical features were studied by retrospective chart review. Results. In each of the sera, autoantibodies that recognize a group of centrosomal proteins were identified, This group included kn own centrosomal autoantigens (pericentrin and pericentriolar material 1 [PCM-1]), the human homolog of a known mouse centrosomal protein, ni nein, which was previously unknown as a human autoantigen, and a novel centrosomal protein (Cep250), Autoantibodies to PCM-1 were the least common (8 of 21 subjects; 38%) while those to ninein, Cep250, and peri centrin occurred at roughly equal frequencies (17 subjects [81%], 17 s ubjects [81%], and 19 subjects [90%], respectively), There was no appa rent correlation between serum autoantibody reactivity and the clinica l diagnosis. Conclusion. Each of the autoimmune sera contained autoant ibodies that reacted with a group of centrosomal proteins, We found th at the centrosomal component ninein, first identified in mice, has a h uman homolog that is an autoantigen, Also, anticentrosomal sera contai ned antibodies to previously undetected centrosomal components, One of these novel antigens was identified and was designated Cep250, Thus, a characteristic of sera reactive with the centrosome is that they con tain antibodies to a group of centrosomal proteins.