THE OFFICIAL NEWS SOURCE OF ACR CONVERGENCE 2022 • NOVEMBER 10-14


Researcher describes simple steps to intercept RA

Rheumatoid arthritis does not appear unannounced. Established, classifiable RA is the result of multiple, sequential pathologic changes over many years that begins with genetic susceptibility and environmental insults and progresses to autoantibody formation and propagation of autoimmunity with an expanding autoantibody profile.

Gerd Burmester, MD
Gerd Burmester, MD

“The genetic profile only predisposes for RA, it does not determine the disease,” said Gerd Burmester, MD, Professor of Medicine at Charité University Hospital, Free University, and Humboldt University in Berlin, Germany. “Autoantibodies and the immune system shape RA, which means we might be successful in battling — even stopping — RA early in the process.”

Dr. Burmester discussed the evolving understanding of RA pathogenesis and new approaches to interrupt disease progression on Saturday, Nov. 6, during the session Immunology Update: Sequential Steps to Intercept RA, which can be viewed by registered meeting participants through March 11, 2022.

RA begins with a genetic susceptibility that combines with environmental factors such as tobacco use, dust exposure, and pathogenic microbial exposures to trigger the formation of autoantibodies, he explained. Anti-citrullinated protein antibodies (ACPAs) have been detected up to 14 years before RA symptoms appear and rheumatoid factor more than 10 years before symptoms.

B cells are important in presenting antigens to T cells, added Dr. Burmester, although the antigens themselves remain unknown. Antigen presentation activates macrophages, which infiltrate into synovial tissue, which can result in joint damage, he explained.

“Citrullination is a key to autoantigenicity. There is no way to produce autoantibodies in a normal person, but in RA, for reasons we do not understand, autoantigenicity can happen. About 70% of RA patients are ACPA-positive,” Dr. Burmester said.

Mechanisms for inducing those anti-modified protein antibodies (AMPAs) include phagocytosis and apoptosis, bacteria, and exposure to tobacco smoke and dust. Smoking and inhaled dust enhance the conversion of arginine to citrulline, boosting the risk of RA by interaction with histocompatibility complex amino acids, primarily positions 11 and 13 in the HLA-DRb1 4-amino acid haplotype.

Bacterial exposure can also contribute to the pathogenesis of RA through both the oral cavity and the gut microbiome. Porphromonas gingivalis, a gram-negative oral anaerobe that can cause inflammation of the periodontium and tooth loss, is known to citrullinate proteins and may be the missing link in ACPA production.

“Not only the flora in the mouth may be important in the pathophysiology and progression of RA, but the gut microbiome is important as well,” Dr. Burmester said. “Approaches to modulate the microbiome like diet, antibiotics, and probiotics could have a role in the management and prevention of RA.”

Once RA has become established, activated macrophages are an attractive therapeutic target, he continued. Longitudinal analyses of RA flares have identified a dominance of monocyte and macrophage infiltration in RA synovial tissue. Populations of preinflammatory mesenchymal (PRIME) cells in peripheral blood is predictive of flare, suggesting that these cells migrate out of the plasma and into the synovium.

“The development of RA requires several factors acting at different points in time in an orchestrated manner. We need to intercept RA at every step of this progression,” Dr. Burmester said. “Smoking is, thus far, the single most important factor for the development of RA, but there are others, including maintaining a healthy weight and diet, good dental hygiene, and remaining vitamin D replete. There are very simple things we can do to reduce the risk of developing RA.”

ACR CONVERGENCE ON DEMAND

Meeting content can be viewed on the virtual platform by registered meeting participants through March 11, 2022. If you were unable to attend the live portion of the virtual meeting, an On-Demand All-Access Pass is still available for purchase.

REGISTER NOW