Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation and joint destruction. As with many autoimmune diseases, RA disproportionally affects females. The development of RA is believed to involve complex interactions that include both environmental and genetic factors, and understanding the contributions of these factors continues to evolve. Many people with RA have detectable circulating autoantibodies—immune proteins that react to an individual’s own proteins—in their serum for years before experiencing any symptoms. The presence of these autoantibodies prior to joint inflammation suggests that the autoimmune process is initiated elsewhere in the body.
Recent studies have pointed to an imbalance of commensal bacteria in mucosal sites as a possible cause of inflammation leading to the initiation of the autoimmune process. In particular, expansion of Prevotella copri in stool was associated with new-onset RA, and additional studies found that people living with RA were more likely to have immune reactivity against P. copri, making this an opportune candidate to further investigate. Given that several previous studies using samples from people with RA reported immune reactivity to a P. copri protein called Pc-p27, this study aimed to further characterize the development and timing of antibody responses to this protein in people at risk for or with RA.
Researchers examined levels of immunoglobulin (Ig)G, an antibody associated with systemic immune responses, and IgA, an antibody associated with immune responses at mucosal sites, in individuals at risk for developing RA, those with early-onset RA, and those with established RA. Overall, people with RA had higher levels of both IgA and IgG anti-Pc-p27 antibodies than their matched healthy controls. When participants were stratified into early and established RA groups, there were notable differences in antibody level trends. Those in the early RA group had trending increases in IgG anti-Pc-p27 antibody levels, while participants with established RA had a significant elevation in IgA anti-Pc-p27 antibody levels. Furthermore, at-risk participants did not have higher IgA or IgG anti-Pc-p27 levels than their matched controls. In the 23 participants in the at-risk group who developed RA during the study, there was no significant increase in either IgA or IgG anti-Pc-p27 antibody levels between the visits before and after receiving their RA diagnosis.
Additional analysis was done to further interrogate the connection between the two known autoantibodies associated with the development of RA, anti-CCP and RF, and the observed differences in IgA and IgG anti-Pc-p27 antibody levels between the RA groups. All RA participants who were positive for both autoantibodies had significantly higher IgA and IgG anti-Pc-p27 antibody levels compared to matched healthy participants in the control group. In addition, at-risk participants who were anti-CCP positive but RF negative had higher IgG anti-Pc-p27 antibody levels than those in the control group.
Taken together, the findings of this study extend the conclusions of previous studies associating immune activity against P. copri with the development of RA. Additional work is needed to understand how P. copri and other microorganisms may contribute to disease pathogenesis, which may ultimately lead to the development of novel interventions to prevent disease in individuals at risk of developing RA. A thorough understanding of the underlying mechanisms that lead to increased susceptibility to autoimmune diseases in women is a critical step in prevention.
References:
Seifert, JA et al. Association of Antibodies to Prevotella copri in Anti–Cyclic Citrullinated Peptide-Positive Individuals At Risk of Developing Rheumatoid Arthritis and in Patients With Early or Established Rheumatoid Arthritis. Arthritis & Rheumatology. DOI 10.1002/art.42370