Q&A: Periodontal Disease and Rheumatoid Arthritis

In this Q&A we feature a conversation with Felipe Andrade, M.D., Ph.D., of the Johns Hopkins University School of Medicine in Baltimore. Dr. Andrade and colleagues published a study in the December 14 issue of Science Translational Medicine in which they describe a connection between a bacterium and periodontal disease and rheumatoid arthritis.

(Please click here to read a summary of the study from Rheumatology Network).

Rheumatology Network:  The relationship between periodontal disease and RA has been well documented over the years. Can you address the significance of your findings?

Dr. Andrade:  I fully agree with the first comment. Indeed, medical investigators have observed a clinical association between periodontal disease (gum diseases) and rheumatoid arthritis since the early 1900s, and over time, researchers have suspected that both diseases may be triggered by a common factor. However, our understanding of how these diseases may be related remained poorly defined. [[{"type":"media","view_mode":"media_crop","fid":"56034","attributes":{"alt":"Felipe Andrade, M.D., Ph.D.","class":"media-image media-image-right","id":"media_crop_9476590038650","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7033","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; float: right;","title":"Felipe Andrade, M.D., Ph.D.","typeof":"foaf:Image"}}]]

Our study identified a common denominator that could explain the association between periodontal disease and rheumatoid arthritis, which is Aggregatibacter actinomycetemcomitans (Aa). Specifically, we found that among many bacteria associated with periodontal disease, Aa has the unique capacity of inducing hypercitrullination, which is suspected of activating the immune system and driving the cascade of events leading to rheumatoid arthritis.

Rheumatology Network:  What is citrullination?

Dr. Andrade:  Citrullination is a process that happens naturally in everyone as a way to regulate the function of proteins. However, in people with rheumatoid arthritis, this process becomes overactive, resulting in hypercitrullination and the abnormal accumulation of citrullinated proteins. This drives the production of antibodies against these proteins that create inflammation and attack the joints in patients with rheumatoid arthritis.

Rheumatology Network:  How prevalent was a Aggregatibacter actinomycetemcomitans (Aa) infection in this group of patients?

Dr. Andrade:  The study additionally demonstrated that that almost half of the patients with rheumatoid arthritis have evidence of infection by Aa, compared with 11% of healthy individuals. More strikingly, exposure to Aa was an important factor for production of antibodies to citrullinated proteins in patients with genetic susceptibility to RA.

Rheumatology Network:  Does the study establish cause and effect?

Dr. Andrade:  While the study provided the first evidence that Aa may be important for RA, both mechanistically (via hypercitrullination) and clinically, we still need experimental demonstration that Aa can directly cause RA. To define cause and effect, further studies are necessary, including the development of novel animal models that could address this question. 

Rheumatology Network:  What can physicians learn from these findings?

Dr. Andrade:  Current treatment with steroids, biologic drugs and physical therapy are effective for reducing or slowing the crippling and painful joint deformities in some, but not all patients with rheumatoid arthritis. This study sheds new light on the longstanding relationship between gum disease and rheumatoid arthritis by identifying hypercitrullination as a common process that unites these two seemingly unrelated conditions. Learning more about how this process starts and causes the immune system to attack proteins in the joint may lead to new ways to treat and even prevent rheumatoid arthritis in the future.

References:

Maximilian F. Konig, Loreto Abusleme, Jesper Reinholdt, et. al. "Aggregatibacter actinomycetemcomitans–induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis," Science Translational Medicine. Dec. 14, 2016. DOI:10.1126/scitranslmed.aaj1921