A reciprocal HLA-Disease Association in Rheumatoid Arthritis and Pemphigus Vulgaris.
Human leukocyte antigens (HLA) have been extensively studied as being antigen presenting receptors, but many aspects of their function remain elusive, especially their association with various autoimmune diseases. Here we discuss an illustrative case of the reciprocal relationship between certainHLA-DRB1alleles and two diseases, rheumatoid arthritis (RA) and pemphigus vulgaris (PV). RA is strongly associated withHLA-DRB1alleles that encode a five amino acid sequence motif in the 70-74 region of the DR beta chain, called the shared epitope (SE), while PV is associated with theHLA-DRB1*04:02allele that encodes a different sequence motif in the same region. Interestingly, whileHLA-DRB1*04:02confers susceptibility to PV, this and other alleles that encode the same sequence motif in the 70-74 region of the DR beta chain are protective against RA. Currently, no convincing explanation for this antagonistic effect is present. Here we briefly review the immunology and immunogenetics of both diseases, identify remaining gaps in our understanding of their association with HLA, and propose the possibility that the 70-74 DR beta epitope may contribute to disease risk by mechanisms other than antigen presentation.
Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
Vincent
V
Van Drongelen
University of Michigan, 5520D MSRB1, SPC 5680, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5680, jholo@umich.edu.
Joseph
J
Holoshitz
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D051184:Desmoglein 3 / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D006680:HLA Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D055261:Immunogenetic Phenomena; D051379:Mice; D010392:Pemphigus / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
C071894:DSG3 protein, human; D051184:Desmoglein 3; D006680:HLA Antigens; D059811:HLA-DRB1 Chains; C553506:HLA-DRB1*04:02 antigen