Rheumatoid arthritis

HLA-DRB1 Shared Epitope

Rheumatoid arthritis is a chronic inflammatory joint disease. Several HLA-DRB1 alleles share a short, similar amino acid sequence in the binding groove, the shared epitope. It is mainly linked to the antibody-positive form of the disease.

What the shared epitope is

Several DRB1 alleles carry a similar short sequence at a decisive point of the binding groove. This favours the presentation of certain, often citrullinated peptides against which the typical ACPA antibodies are directed. Thus a shared structural feature links different alleles to the same risk.

Context

The shared epitope raises risk but is neither necessary nor sufficient. Environmental factors such as smoking and other genes contribute. Genome shows the DRB1 typing; assessment belongs in the clinical context.

What Genome measures. Whether HLA-DRB1 alleles with the shared epitope motif (such as DRB1*04:01, *04:04, *01:01) are present in the typing, as risk context.

Related topics

HLA and autoimmunityHLA typing

Sources

  1. 1Gregersen et al., 1987 The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis & Rheumatism 30:1205–1213. doi.org/10.1002/art.1780301102
  2. 2Raychaudhuri et al., 2012 Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nature Genetics 44:291–296. doi.org/10.1038/ng.1076