IMR Press / FBL / Volume 22 / Issue 5 / DOI: 10.2741/4524

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.


A reciprocal HLA-disease association in rheumatoid arthritis and pemphigus vulgaris

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1 Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA

Academic Editor: Joseph Holoshitz

Front. Biosci. (Landmark Ed) 2017, 22(5), 909–919;
Published: 1 January 2017
(This article belongs to the Special Issue The pathogenesis of rheumatoid arthritis)

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 certain HLA-DRB1 alleles and two diseases, rheumatoid arthritis (RA) and pemphigus vulgaris (PV). RA is strongly associated with HLA-DRB1 alleles 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 the HLA-DRB1*04:02 allele that encodes a different sequence motif in the same region. Interestingly, while HLA-DRB1*04:02 confers 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.

Pemphigus Vulgaris
Rheumatoid Arthritis
Shared Epitope
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