MHC class II gene associations with autoantibodies to U1A and SmD1 proteins

Autoantibodies against U small nuclear ribonucleoproteins (snRNP) are frequ ently present in the serum of patients with systemic rheumatic diseases, an d have been reported to be associated with HLA-DR and -DQ genes. To better define the role of HLA genes in the production of such antibodies, we studi ed immunogenetic associations with autoantibodies reacting with U1 RNP, U1A and SmD1 proteins, and synthetic peptides containing immunodominant linear epitopes of these proteins. Only two out of the 15 overlapping peptides of U1A (i.e, peptides 35-58 and 257-282) and three of 11 peptides of SmD1 (i. e. peptides 1-20, 44-67 and 97-119) were significantly recognized by patien ts' sera selected on the basis of their antibody positivity with RNP in imm unodiffusion. The distribution of DRB1, DQB1 and DPB1 alleles among the ant i-RNP antibody-positive patients (n = 28) and healthy control subjects was similar. Antibodies against U1A (tested in Western immunoblotting with HeLa cell extracts) were positively associated to DRB1*06 allele; antibodies re acting with SmD1 peptide 44-67 were negatively associated to DRB1*02 and DQ B1*0602 alleles. No association was found between DPB1 alleles anal antibod ies reacting with U1A and SmD1 antigens. This first study reporting an asso ciation between autoantibodies reacting with U1A and SmD1 proteins land pep tides of these proteins), and immunogenetic markers suggest that the produc tion of antibody subsets directed against different components (or regions of these proteins) bound to the same snRNP particle is associated with dist inct MHC class II alleles.