Associations of MHC class II alleles in Norwegian primary Sjögren's syndrome patients: implications for development of autoantibodies to the Ro52 autoantigen.

Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by dryness of the eyes and mouth. Currently, the highly polymorphic major histocompatibility complex (MHC) genes are the best documented genetic risk factor for the development of autoimmune disease. We examined the MHC class II alleles DRB1, DRB3, DRB4, DRB5, DQA1 and DQB1 in a group of Norwegian pSS patients and compared with a group of healthy controls. Because a number of studies have shown that some of the MHC class II alleles are not associated with the disease as a whole, but rather to the development of autoantibodies, anti-Ro52 autoantibodies in serum were measured and compared to MHC class II allele status. A clear association with pSS was detected for the DRB10301 and DRB30101 alleles, but these alleles were more closely associated with the presence of anti-Ro52 autoantibodies than with pSS itself. Moreover, the DQA10501 and DQB10201 alleles were only associated with the presence of anti-Ro52 autoantibodies. This study shows that the production of anti-Ro52 autoantibodies in pSS is associated with the DRB10301, DRB30101, DQA10501 and DQB10201 alleles which are in strong linkage disequilibrium.