Highlights of the American College of Rheumatology
2010 Scientific Meeting

It might sound a bit odd, but what ALR Scientific Advisory Board Chair Mary (Peggy) K. Crow, MD found most interesting from this year’s meeting had to do with rheumatoid arthritis (RA). Specifically, the possibility that bacterial infections in the mouth and stomach could trigger the disease. So why highlight it here when our focus is lupus? “Because it may also apply to lupus in the end,” she said, given that systemic lupus erythematous (SLE) and rheumatoid arthritis share several genetic markers.

Two studies at the ACR meeting focused on bacteria called Porphyromonas gingivalis (P. gingivalis), which causes gum disease. Previous studies have found that people with RA are far more likely to have evidence of P. gingivalis infection than those without the disease. Now researchers have found that the bacteria trigger a process called citrulination, which changes the structure of certain proteins, resulting in the anti-citrullinated protein (ACP) antibodies that are a hallmark of RA.ⁱ Another study used DNA sequencing to prove that RA patients have higher levels of Prevoltellacaeae bacteria in their gut than healthy patients, bacteria thought to induce the differentiation of inflammatory Th17 cells in the intestine.ⁱⁱ

“The overall theme is that there is value in considering how environmental microbes such as bacteria and viruses can promote autoimmune disease,” Dr. Crow said, “turning on and off the immune system in ways they shouldn’t.”

Of more interest to the lupus community, she said, is the growing science regarding the role of nucleic acids like DNA and RNA in driving immune responses through proteins called toll-like receptors (TLR). These molecules recognize autoantigens that contain DNA and RNA and can trigger inflammatory responses from interferon alpha, resulting in more damage. In addition, she noted, TLR activation is an important mechanism in promoting B cell activation. The ALR has funded several investigators who are focusing on ways to inhibit TLRs from triggering interferon alpha production.

“None of this was even thought of 10 or 12 years ago,” she said. “I feel like we’ve honed in on a lot of the key mechanisms associated with lupus, particularly the role of TLRs and nucleic acids. For years, everyone knew that anti-DNA antibodies target the proteins associated with lupus, but a big advance in the last 10 years has been our ability to understand that they don’t just target autoantibodies; they play a role in the autoimmune response. The whole concept suggests all sorts of potential drug targets that can come from controlling the ability of nucleic acids to associate with TLRs.”

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The 2010 American College of Rheumatology Meeting Special Report was made possible in part by generous support from Biogen Idec, Genentech and Johnson & Johnson.

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