title: Autoantibodies to a group of centrosomal proteins in human autoimmune sera reactive with the centrosome.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The University of Calgary, Alberta, Canada.
authors.forename: G J
authors.initials: GJ
authors.lastname: Mack
authors.forename: J
authors.initials: J
authors.lastname: Rees
authors.forename: O
authors.initials: O
authors.lastname: Sandblom
authors.forename: R
authors.initials: R
authors.lastname: Balczon
authors.forename: M J
authors.initials: MJ
authors.lastname: Fritzler
authors.forename: J B
authors.initials: JB
authors.lastname: Rattner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000032:analysis*; D001324:Autoantigens / Q000235:genetics; D001327:Autoimmune Diseases / Q000097:blood* / Q000276:immunology*; D001483:Base Sequence; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D018385:Centrosome / Q000276:immunology*; D002648:Child; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000276:immunology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D019204:GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D009687:Nuclear Proteins
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D018797:Cell Cycle Proteins; C111329:CEP250 protein, human; D003598:Cytoskeletal Proteins; C512806:NIN protein, human; C099035:Nin protein, mouse; D009687:Nuclear Proteins; D019204:GTP-Binding Proteins