A pathogen linked to periodontal disease might trigger production of autoantigens that set off and sustain inflammatory immune responses in the joints in rheumatoid arthritis (RA), according to new research published online December 14 in Science Translational Medicine.
The research team was led by Maximilian F. Konig, MD, and Felipe Andrade, MD, PhD, both from the Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
The landmark study supports the hypothesis that bacterial pathogens play key roles in some cases of RA. The new data are expected to catalyze research efforts in primary prevention and in treatment strategies not based on immunosuppression. The findings also open a new window onto the interaction between RA genetic susceptibility and environmental triggers.
Dr Andrade, who is associate professor of medicine at Johns Hopkins University, told Medscape Medical News that these findings provide concrete evidence for a mechanism through which a pathogen might trigger the autoimmune and mucosal changes associated with RA.
Dr Konig, who is now at Massachusetts General Hospital, Boston, said in a news release, "This research may be the closest we've come to uncovering the root cause of RA."
The pathogen perpetrator is Aggregatibacter actinomycetemcomitans (Aa), formerly known as Haemophilus actinomycetemcomitans. Aa is a Gram-negative, facultative anaerobe found in 62% of chronic periodontitis cases.
The research team focused on possible effects of Aa infections on citrullination (conversion of the amino acid arginine in a protein into the amino acid citrulline), part of the normal machinery for regulating protein function. Citrullination creates novel epitopes and "neoantigens" on common proteins, which in turn induce autoantibodies and are removed by the immune system.
In RA, citrullination can become excessive and mediates damage to the joint tissues.
Anticitrullinated protein antibodies are a hallmark of RA, and many are present early in the disease process. These antibodies are associated with erosive joint destruction and greater disease activity, and positivity at the time of diagnosis is a predictor of more aggressive disease.