Autoantibodies to fibrillarin in systemic sclerosis (scleroderma). An immunogenetic, serologic, and clinical analysis
Article first published online: 12 DEC 2005
Copyright © 1996 American College of Rheumatology
Arthritis & Rheumatism
Volume 39, Issue 7, pages 1151–1160, July 1996
How to Cite
Arnett, F. C., Reveille, J. D., Goldstein, R., Pollard, K. M., Leaird, K., Smith, E. A., Leroy, E. C. and Fritzler, M. J. (1996), Autoantibodies to fibrillarin in systemic sclerosis (scleroderma). An immunogenetic, serologic, and clinical analysis. Arthritis & Rheumatism, 39: 1151–1160. doi: 10.1002/art.1780390712
- Issue published online: 12 DEC 2005
- Article first published online: 12 DEC 2005
- Manuscript Accepted: 14 FEB 1996
- Manuscript Received: 4 DEC 1995
- Scleroderma Research Foundation and the RGK Foundation. Grant Number: R-29AR-39325
- Medical Research Council of Canada. Grant Number: MT-10884
- NIH. Grant Numbers: R-29A-I32155, P-60AR-40770
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.