A potential mechanism by which rheumatoid arthritis, an autoimmune disease, may be triggered by microbial infection is suggested in a paper in Nature Communications this week.
Rheumatoid arthritis (RA), a chronic disease affecting the joints, occurs when the immune system launches an attack on the body. Genetics are known to play a role, with variations in immune system-related genes predisposing to or protecting from the condition. Autoantibodies (antibodies directed at an individual’s own proteins) targeting specific “citrullinated” proteins are common in RA patients. Citrullinated proteins are those where an arginine amino acid has been converted to a citrulline amino acid.
Rene Toes and colleagues now show that one of these citrullinated proteins called vinculin, found in the joints of RA patients, is targeted by autoantibodies and by immune system cells. The authors discovered that the immune response does not occur in RA patients who carry a certain protective genetic variant. They also show that T cells recognise a specific amino acid sequence within the vinculin molecule that is also found in many microbes. This, along with other lines of evidence from previous studies, hints at a possible role for microbes in the disease process.