SPECIFIC HLA-DQA AND HLA-DRB1 ALLELES CONFER SUSCEPTIBILITY TO SJOGRENS-SYNDROME AND AUTOANTIBODY PRODUCTION

Primary Sjogren's syndrome (1-degrees SS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the salivary glands and autoantibody production. In order to identify genetic factors that play a role in pathogenesis and predict extent of disease, we used Southern blot and polymerase chain reaction (PCR) methods to detect polymorphisms of the HLA-DRB1 (DR), HLA-DRB3 (DRw52), and HLA-DQA1 genes among 75 Caucasoid 1-degrees SS patients and 150 Caucasoid controls living in the same geographic region of Southern California. We found significantly increased frequency of HLA-DR3 (P < .001), HLA-DW52a (P < .001), and HLA-DQA4 (P < .05), in comparison to normal controls. Also, an increased frequency of heterozygosity for HLA-DQA1/DQA4 (P < .05) was present among 1-degrees SS patients. Autoantibodies to SS-A and to SS-B were significantly associated with DR3 (P <.001), HLA-DQA4, (P < .05), and DQA4/DQA1 heterozygotes (P < .01). Among the 1-degrees SS patients, clinical and laboratory features such as hypergammaglobulinemia, symmetric peripheral neuropathy, and hypothyroidism were significantly associated with HLA-DR3 (P < .01) but not with HLA-DR2 (P > .10). In comparison, 1-degrees SS patients with leukocytoclastic vasculitis were more frequently HLA-DR2 (P < .05). These results using PCR methods confirm and extend prior studies that have used serologic methods.