AUTOANTIBODIES TO FIBRILLARIN IN SYSTEMIC-SCLEROSIS (SCLERODERMA) - AN IMMUNOGENETIC, SEROLOGIC, AND CLINICAL ANALYSIS

Objective. To determine the frequency, clinical associations, and any major histocompatibility complex correlations of antifibrillarin antib odies in patients with systemic sclerosis (SSc). Methods. Antifibrilla rin antibodies were determined by indirect immunofluorescence, immunob lotting, and immunoprecipitation, and HLA class II alleles by DNA olig otyping, in a large cohort of SSc patients. Results. Antifibrillarin w as found in 8% of 335 SSc sera and was significantly more common in bl acks (16%) than whites (5%), in males (33%) than females (14%), and in patients with cardiac, renal, or gut involvement. The HLA class II ha plotype DRB11302, DQB1*0604 was found significantly more frequently i n SSc patients with antifibrillarin compared with race-matched 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 antifib rillarin-positive patients had 2 of these HLA-DQB1 alleles, a highly s ignificant difference from both race-matched normal controls and antif ibrillarin-negative SSc patients. Conclusion. Antifibrillarin, althoug h an infrequent nucleolar autoantibody, is a marker for severe SSc, es pecially in blacks and males, and is strongly associated with a unique HLA haplotype, as well as with combinations of certain HLA-DQB1 allel es.