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The immunogenetics of Sjögren's syndrome.

The fact that patients with SS, either primary or associated with another connective tissue disease, show a striking tendency toward familial aggregation of SS, other autoimmune disease and autoantibodies suggest a role for genetic factors in the pathogenesis of this disease. What these factors are is as yet not known; however, it is clear that autoantibodies found in high frequency in SS, specifically anti-Ro and anti-La, are associated with HLA class II alleles, found at the HLA-DQA1 and DQB1 loci, which have in common the presence of specific amino acid residues that are found in the second hypervariable region of the first (outermost) domain. Additional roles for T-lymphocyte receptor and immunoglobulin genes are also suggested. Family studies, however, indicate the presence of an additional autosomal dominant gene(s), not linked to HLA or immunoglobulin heavy or light chain genes, in predisposition to SS. Identification of this additional genetic factor(s) should provide important clues in the pathogenesis of SS.

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