ARTICLE EXTRAS
Recently, Lars Klareskog at the Karolinska Institute and his colleagues described a strong gene-environment interaction in a subset of people with rheumatoid arthritis (RA) (L. Klareskog et al., "Genes, environment, and immunity in the development of rheumatoid arthritis," Curr Opin Immunol, 18:650-5, 2006.) "It was well established that smoking is a risk factor in RA, but no one knew why," says Klareskog. "It was also known that certain HLA-DRB1 variants are risk genes, but we didn't know which reactions they were involved in," he explains. As the third piece of the puzzle, autoimmunity against antigens that become citrullinated (changing the amino acid arginine to citrulline) was specifically linked to certain forms of RA. According to Klareskog, long-term exposure to cigarette smoke might trigger mechanisms that promote the citrullination of proteins, which increases their immunogenicity, especially in individuals who carry the shared epitope variants of the HLA-DRB1 genes.
