Nitric oxide signaling triggered by the rheumatoid arthritis shared epitope: a new paradigm for MHC disease association?
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.
Holoshitz
Joseph
J
Department of Internal Medicine, University of Michigan Medical Center, 5520 MSRB I, Ann Arbor, Michigan 48109-0680, USA. jholo@umich.edu
Ling
Song
S
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism*; D000939:Epitopes / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology*; D006801:Humans; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism*; D015398:Signal Transduction
D000939:Epitopes; D006649:Histocompatibility Antigens; D009569:Nitric Oxide