Open AccessAutoantibodies to a group of centrosomal proteins in human autoimmune sera reactive with the centrosome
Author(s) -
Mack Gary J.,
Rees Jennifer,
Sandblom Olof,
Balczon Ronald,
Fritzler Marvin J.,
Rattner J. B.
Publication year - 1998
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/1529-0131(199803)41:3<551::aid-art22>3.0.co;2-x
Subject(s) - autoantibody , centrosome , biology , immunofluorescence , antigen , immunology , microbiology and biotechnology , antibody , blot , cell cycle , cell , genetics , gene
Objective Human autoantibodies reacting with protein components of the microtubule organizing center of the cell, the centrosome, are rare and have not been extensively studied. We therefore investigated the number, 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 reactivity with the centrosome throughout the cell cycle, to screen a HeLa complementary DNA (cDNA) (expression) library. Positive cDNA clones were sequenced and classified as encoding either known centrosomal autoantigens, known centrosomal proteins but unknown as human autoantigens, or previously unknown centrosomal antigens. To investigate whether these centrosomal autoantibody classes were characteristic of centrosomal‐reactive sera, sera from 21 subjects with centrosomal reactivity by indirect immunofluorescence were characterized by Western blotting for reactivity to recombinant protein from each of the classes of centrosomal 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 known centrosomal autoantigens (pericentrin and pericentriolar material 1 [PCM‐1]), the human homolog of a known mouse centrosomal protein, ninein, 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 pericentrin occurred at roughly equal frequencies (17 subjects [81%], 17 subjects [81%], and 19 subjects [90%], respectively). There was no apparent correlation between serum autoantibody reactivity and the clinical diagnosis. Conclusion Each of the autoimmune sera contained autoantibodies that reacted with a group of centrosomal proteins. We found that the centrosomal component ninein, first identified in mice, has a human homolog that is an autoantigen. Also, anticentrosomal sera contained 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 contain antibodies to a group of centrosomal proteins.