Studies of HLA-DR and DQ alleles in systemic sclerosis patients with autoantibodies to RNA polymerases and U3-RNP (fibrillarin).

To determine the clinical and immunogenetic features of systemic sclerosis (SSc) patients with anti-RNA polymerase (RNAP) or anti-fibrillarin antibodies. DNA typing for HLA-DR and DQ alleles was performed in 292 patients with SSc, including 81 with anti-RNAP and 24 with anti-fibrillarin antibodies. The remaining patients had anti-topoisomerase I (anti-topo I; 71), anti-centromere (ACA; 56), anti-Th/To (28), or other antinuclear (32) antibodies. Significant associations were observed in the patients with anti-topo I, ACA, and anti-Th/To antibodies, similar to those previously reported. No significant HLA associations were detected in the 81 patients with anti-RNAP. although weak associations were noted when this group was subdivided on the basis of immunofluorescence staining pattern; i.e., HLA-DR4 was increased in patients with strong nucleolar staining and HLA-DR3 was more frequent in patients with nucleoplasm staining only. No HLA-DR or DQ associations were observed in 24 patients with anti-fibrillarin antibodies. The identification of HLA associations in SSc patients with anti-RNAP antibodies may only be possible when the individual antibody specificities recognized by these sera are identified. It may then be possible to classify these patients into distinct clinical and immunogenetic subgroups.