The role of common protective alleles HLA-DRB1*13 among systemic autoimmune diseases.
Associations between human leukocyte antigen (HLA) and susceptibility to systemic autoimmune diseases have been reported. The predisposing alleles are variable among ethnic groups and/or diseases. On the other hand, some HLA alleles are associated with resistance to systemic autoimmune diseases, including systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis. Interestingly, DRB1*13 alleles are the protective alleles shared by multiple autoimmune diseases. DRB1*13:01 allele is protective in European populations and DRB1*13:02 in Japanese. Because alleles in multiple HLA loci are in strong linkage disequilibrium, it is difficult to determine which of the protective alleles is functionally responsible for the protective effects. Thus far, association studies suggested that DRB1*13:02 represents at least one of the causally associated protective factors against multiple systemic autoimmune diseases in the Japanese population. The protective effect of DRB1*13 alleles appears to overcome the predisposing effect of the susceptible alleles in heterozygous individuals of DRB1*13 and the susceptible allele. A gene dosage effect was observed in the associations of DRB1*13:02 with the protection from systemic autoimmune diseases; thus homozygous individuals are more effectively protected from the systemic autoimmune diseases than heterozygotes. DRB1*13:02 also confers protection against organ-specific autoimmune diseases and some infectious diseases. Several hypotheses can be proposed for the molecular mechanisms of the protection conferred by DRB1*13, some of which can explain the dominant effect of DRB1*13 molecules over the susceptible alleles, but the actual protective function of DRB1*13 requires further study. Understanding of the protective mechanisms of DRB1*13 may lead to the identification of targets for the curative treatment of systemic autoimmune diseases.
Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.|Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Sagamihara, Japan.
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0000-0002-4022-0767
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Furukawa
Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.|Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Sagamihara, Japan.
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Oka
Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
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0000-0002-6776-5580
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Tsuchiya
Department of Rheumatology, National Hospital Organization Sagamihara National Hospital, Sagamihara, Japan.|Department of Rheumatic Diseases, Tokyo Metropolitan Tama Medical Center, Fuchu, Japan.
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Shimada
Department of Rheumatology, National Hospital Organization Sagamihara National Hospital, Sagamihara, Japan.
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Hashimoto
Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Sagamihara, Japan.
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Tohma
Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
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A
Kawasaki
D001327:Autoimmune Diseases / Q000276:immunology* / Q000517:prevention & control*; D059811:HLA-DRB1 Chains / Q000276:immunology*; D006801:Humans; D020011:Protective Agents / Q000008:administration & dosage*
D059811:HLA-DRB1 Chains; D020011:Protective Agents