Open AccessAutoantibodies to fibrillarin in systemic sclerosis (scleroderma). An immunogenetic, serologic, and clinical analysis
Author(s) -
Arnett Frank C.,
Reveille John D.,
Goldstein Rose,
Pollard K. Michael,
Leaird Kimberly,
Smith Edwin A.,
Leroy E. Carwile,
Fritzler Marvin J.
Publication year - 1996
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.1780390712
Subject(s) - autoantibody , immunology , haplotype , scleroderma (fungus) , serology , medicine , allele , human leukocyte antigen , fibrillarin , antibody , biology , antigen , genetics , gene , nucleus , inoculation , psychiatry , nucleolus
Objective . To determine the frequency, clinical associations, and any major histocompatibility complex correlations of antifibrillarin antibodies in patients with systemic sclerosis (SSc). Methods . Antifibrillarin antibodies were determined by indirect immunofluorescence, immunoblotting, and immunoprecipitation, and HLA class II alleles by DNA oligotyping, in a large cohort of SSc patients. Results . Antifibrillarin was found in 8% of 335 SSc sera and was significantly more common in blacks (16%) than whites (5%), in males (33%) than females (14%), and in patients with cardiac, renal, or gut involvement. The HLA class II haplotype DRB1 * 1302 , DQB1 * 0604 was found significantly more frequently in SSc patients with antifibrillarin compared with racematched normal controls and 260 SSc patients without antifibrillarin. In addition, 1 or more of the HLA–DQB1 alleles * 0604 , * 0301 , * 0602 , and/or * 0302 was found in all antifibrillarin‐positive patients, and 62% of the antifibrillarin‐positive patients had 2 of these HLA–DQB1 alleles, a highly significant difference from both race‐matched normal controls and antifibrillarin‐negative SSc patients. Conclusion . Antifibrillarin, although an infrequent nucleolar autoantibody, is a marker for severe SSc, especially in blacks and males, and is strongly associated with a unique HLA haplotype, as well as with combinations of certain HLA–DQB1 alleles.