The rheumatoid arthritis HLA-DRB1 shared epitope

Curr Opin Rheumatol. 2010 May;22(3):293-8. doi: 10.1097/BOR.0b013e328336ba63.


Purpose of review: To update progress made between December 2008 and November 2009 on the role of the rheumatoid arthritis (RA)-shared epitope in the cause and pathogenesis of RA.

Recent findings: New evidence has been recently presented to suggest that noninherited human leukocyte antigens (HLAs) originating through pregnancy or exposure to maternal antigens in utero could contribute to RA development in shared epitope-negative women. An interaction between smoking and shared epitope-coding non-*04 HLA-DRB1 alleles (particularly HLA-DRB1*01 and HLA-DRB1*10) was formally established for the first time. Progress has been made in determining the relative contributions and the interaction of the shared epitope, PTPN22 and smoking in conferring the risk of anticitrullinated protein antibodies-positive and negative RA. The autoantigen that anticitrullinated protein antibodies recognize in a significant number of RA patients has been identified as citrullinated alpha-enolase and the importance of genetic factors in anticitrullinated protein antibodies-negative RA has been highlighted. Additionally, associations of RA risk with several new genetic markers have been reported. Among them: two new major histocompatibility complex, non-DRB1 loci, a polymorphism marker in major histocompatibility complex class I polypeptide-related sequence A, an allele of the Fcgamma receptor, a polymorphism marker in the beta2-adrenergic receptor and a low-inducible allele of the cytochrome P450 subtype 1A2.

Summary: Although the mechanistic basis of shared epitope-RA association remains an enigma, observations made during the last year shed new light on the conditions in which the shared epitope - alone or in combination with other genes or environmental factors - affects the risk of RA and the phenotype of the disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / physiopathology
  • Autoantibodies / genetics
  • Autoantibodies / immunology
  • Biomarkers / analysis
  • Epitopes / genetics*
  • Epitopes / immunology*
  • Genetic Markers / genetics
  • HLA-DR Antigens / genetics*
  • HLA-DR Antigens / immunology*
  • HLA-DRB1 Chains
  • Humans
  • Polymorphism, Genetic / genetics
  • Polymorphism, Genetic / immunology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / immunology


  • Autoantibodies
  • Biomarkers
  • Epitopes
  • Genetic Markers
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22