Nitric oxide signaling triggered by the rheumatoid arthritis shared epitope: a new paradigm for MHC disease association?

Ann N Y Acad Sci. 2007 Sep;1110:73-83. doi: 10.1196/annals.1423.009.


Many immune-mediated diseases are associated with particular MHC class I or class II alleles. In rheumatoid arthritis (RA-shared), the vast majority of patients possess HLA-DRB1 alleles encoding a shared epitope, which is a five-amino acid sequence motif in positions 70-74 of the HLA-DRbeta chain. The mechanistic basis for this association is unknown. Here we discuss recent evidence suggesting that the shared epitope may act as an allele-specific ligand that triggers increased nitric oxide (NO) production in opposite cells with resultant immune dysregulation. We propose that by doing that, the RA-shared shared epitope may form an unintended bridge between the innate and adaptive immune systems, thereby allowing aberrant signaling events that could trigger disease.

Publication types

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

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism*
  • Epitopes / immunology*
  • Histocompatibility Antigens / immunology*
  • Humans
  • Models, Biological
  • Nitric Oxide / metabolism*
  • Signal Transduction*


  • Epitopes
  • Histocompatibility Antigens
  • Nitric Oxide