In patients with rheumatoid arthritis (RA), self-reactive T cell responses cause inflammation and progressive damage to synovial joints. Although genetic risk factors for RA have been identified, environmental causes are also thought to play a role in the onset of RA. Recent work suggests that the disease is initially triggered by immune responses to gut bacteria, but how autoimmunity of intestinal origin plays a role in RA-linked autoimmune responses is unclear.
A study led by Annalisa Pianta at Massachusetts General Hospital describes two proteins derived from common types of gut bacteria that evoke immune responses in RA patients. N-acetyl-glucosamine-6-sulfatase (GNS) and filamin A (FLNA) were identified as autoantigens that produce responses from both T and B cells in over 50% of RA patients, but not healthy controls or patients with other rheumatic diseases. Although GNS and FLNA antigens were discovered in the synovial joint fluid in RA-affected joints, GNS and FLNA proteins show remarkable similarity to proteins produced by common classes of intestinal bacteria.