POLYMORPHISMS OF HLA CLASS-II GENES AND AUTOIMMUNE RESPONSES TO RO SS-A-LA/SS-B AMONG JAPANESE SUBJECTS/

Objective. To investigate HLA class II allele associations with autoan tibody responses to Ro/SS-A and La/SS-B among Japanese subjects. Metho ds. Haplotype and allele distributions, along with molecular polymorph isms, of HLA class II genes were analyzed by polymerase chain reaction -restriction fragment length polymorphism in 41 Japanese women with pr ecipitating autoantibodies to Ro/SS-A and/or La/SS-B, Results. Among w omen with both Ro/SS-A and La/SS-B antibodies, the HLA class II haplot ype DRB108032/DQA1*0103/DQB1*0601 and DRB1*08032 allele showed signif icantly increased frequencies compared with patients with anti-Ro/SS-A alone or with normal controls. All women with both anti-Ro/SS-A and a nti-La/SS-B, but not those with anti-Ro/SS-A alone, carried DRB1 allel es that shared the same amino acid residues at positions 14-31 and 71 of the hypervariable regions of the DRB1 chain. All anti-Ro/SS-A posit ive women carried 1 or 2 alleles of DQB106 and DQB1*03 subtypes that shared the same amino acid residues at positions 71-77 of the DQB1 cha in. HLA class II allele distributions did not differ among 3 anti-Ro/S S-A positive groups with different disease expressions, i.e., patients with systemic lupus erythematosus, patients with primary Sjogren's sy ndrome, and women with no apparent symptoms of rheumatic disease. Conc lusion. HLA class II allele distributions differ among anti-Ro/SS-A po sitive subjects according to the presence or absence of coexisting ant i-La/SS-B antibodies, but not according to disease expression. Our fin dings suggest that different HLA class II molecules might control the development of anti-Ro/SS-A and/or anti-La/SS-B antibodies in the auto immune response to the Ro/SS-A-La/SS-B complex.