Immune Reaction to Gut Bacterium May Trigger Rheumatoid Arthritis

Rheumatoid arthritis is an autoimmune condition in which the immune system attacks the tissues of the joints, especially in the knees, hands, and wrists. This causes inflammation and painful swelling.

People with rheumatoid arthritis often experience mild symptoms for the first time in their 60s, which then gradually worsen over time. However, antibodies that target the body’s own tissues may circulate in the blood for several years before the onset of rheumatoid arthritis. Prevotella copri (Pc), a gut commensal, has been reported to be an immune relevant organism in individuals with rheumatoid arthritis (RA).

A team of Medical Scientists at the University of Colorado Denver (Aurora, CO, USA) hypothesized immune reactivity to Pc may be found in additional RA populations and potentially in individuals at-risk for developing RA. The study compared 98 patients with established rheumatoid arthritis, and 67 people at high risk of developing rheumatoid arthritis, with equal numbers of matched, healthy controls.

Serum levels of IgA and IgG anti-Pc-p27, an immunogenic Pc protein, were analyzed in study participants at-risk for the development of RA, those who transitioned to RA, in those with early RA (< one year of disease), and in those with established RA, compared to matched controls. Additionally, levels of anti-Pc-p27 antibodies were evaluated in individuals stratified by RA-related autoantibody status.

Serum samples were tested for the following autoantibodies: anti-CCP3 (IgG ELISA; Inova Diagnostics, San Diego, CA, USA), and RF isotypes IgA and IgM by ELISA (Quanta Lite kits, Werfen, Bedford, MA, USA). DNA from buffy coat samples was genotyped for the presence of HLA alleles containing the shared epitope (SE). Participants were tested for IgA and IgG antibody responses to Pc-p27, as determined by ELISA.

The investigators reported that overall, participants with RA had significantly higher levels of IgA anti-Pc-p27 antibodies and trends towards higher levels of IgG anti-Pc-p27 antibodies when compared to their matched controls. When stratified by early versus established RA, early RA participants had median values of IgG anti-Pc-p27 antibodies that were overall higher, whereas median values of IgA anti-Pc-p27 were statistically significantly higher in participants with established RA, compared with their matched controls. In the autoantibody specific analyses, the at-risk population with anti-CCP antibodies, but not Rheumatoid Factor (RF), demonstrated trends towards increased levels of IgG anti-Pc-p27. Additionally, RA participants who were CCP+/RF+ had significantly increased levels of IgA anti-Pc-p27 antibodies and a trend toward levels of IgG anti-Pc-p27 antibodies when compared to their matched controls.

Jennifer A. Seifert, MPH, the corresponding author of the study, said, “Our hope is that these findings can help to further elucidate the complex causative role of bacterial commensals in people who are at risk of developing rheumatoid arthritis and in those with rheumatoid arthritis so that targeted therapies can be developed with the goals of providing better treatment and ultimately, prevention of the disease.”

The authors concluded that at-risk participants and those with early RA had overall higher levels of IgG anti-Pc-p27 antibodies and those with established RA had significantly increased levels of IgA anti-Pc-p27 antibodies. The study was published on October 19, 2022 in the journal Arthritis and Rheumatology.

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