Immunogenetics of Sjögren's syndrome.
The etiology for SS remains unknown where multifactorial influences contribute to the pathogenesis of subsequent development of the disease. The genetic influence is also multifactorial and the data suggests a familial component indicative of autosomal-dominant genes as well as genetic contributions associated with class-I and class-II HLA alleles. Various auto-antibodies found with increased frequency in SS (anti-Ro and anti-La) were shown to be associated with HLA class-II alleles at the DQA1 and DQB1 loci that were also found to have in common specific amino acid residues (10). Ethnic groups have also been studied and show varying HLA associations with primary SS. Multiple ethnic groups, however, share a DQ allele supporting the idea that the majority of SS patients carry a common allele which may predispose to primary SS. In some cases, the HLA-DR antigen may be induced and cause to appear on epithelial cells where they present antigen to CD 4+ T-cells, which then go on to aid in the destruction of salivary gland epithelial cells specifically. The further elucidation of disease associations as well as possible immunogenetic pathogenic mechanisms may help to explain the causes for the development of various autoimmune diseases such as Sjögren's Syndrome. This may eventually result in the ability to immunomodulate these abnormal immune responses. In so doing, an approach to treatment by genetic engineering may also be possible once a further understanding of the genetic influences and mechanisms in the causation of autoimmune disease is further elucidated.
Kassan
S S
SS
University of Colorado Health Sciences Center, Denver, Colorado, USA.
D000483:Alleles; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D012469:Salivary Glands / Q000276:immunology; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II