PARIS – A set of genetic polymorphisms is beginning to allow researchers to predict which patients with rheumatoid arthritis will have a severe disease course, as well as determine their response to treatment and risk of death.
Changes in amino acids at positions 71 and 74 of the HLA-DRB1 gene, which are a part of the "shared epitope" that is already known to increase genetic susceptibility for rheumatoid arthritis, as well as a new polymorphism at position 11 of the HLA-DRB1 gene that is outside the shared epitope, are key to this effort. These polymorphisms predicted the radiologic outcome of rheumatoid arthritis patients, response to anti-tumor necrosis factor therapy, and mortality in an analysis of blood samples from three independent multicenter, prospective cohort studies. The three polymorphisms defined 16 haplotypes whose effects on RA susceptibility range from protective to increasing risk and were perfectly correlated with the observed levels of disease susceptibility.
Further studies will be necessary to validate the associations observed with the sets of polymorphisms, said Dr. Sebastien Viatte, first author of the study and a research fellow at the Centre for Musculoskeletal Research at the University of Manchester (England). Nonetheless, the results are an important step in showing that "genetics can be used to predict disease outcomes and is ... likely to enter the clinic within 5-10 years," he said in a video interview at the annual European Congress of Rheumatology.