A recent study has revealed compelling evidence linking immune responses to a newly identified species of gut bacteria to the development of rheumatoid arthritis (RA), a prevalent autoimmune disease. The groundbreaking findings from this research have been published in the esteemed journal Science Translational Medicine.
Individuals who have rheumatoid arthritis (RA) experience an attack on their joints by their own antibodies and T cells, primarily affecting the hands, wrists, and knees. This, in turn, leads to inflammation, pain, and swelling in the lining of the joints. As time passes, RA progresses and causes irreversible damage to the joint tissues, resulting in chronic pain, loss of function, and deformities. Despite extensive efforts, scientists have yet to determine the exact cause of RA, particularly in its early stages.
Research on rheumatoid arthritis (RA) has primarily aimed to understand the triggers for the development of antibodies and T cells that attack the joints. Multiple studies have suggested that the production of antibodies targeting the joints initiates at mucosal surfaces, such as the mouth, airways, and gut, over a decade before symptoms manifest. Furthermore, it is believed that bacteria present in these areas may stimulate this antibody production. However, the specific bacterial culprit has remained unidentified until now.
In the recent study, researchers conducted an investigation on individuals at risk for rheumatoid arthritis (RA). They specifically examined a group of cells called plasmablasts, responsible for secreting antibodies. Interestingly, the antibodies produced by these cells demonstrate an ability to recognize certain bacteria present in the gut microbiome of these individuals. Remarkably, the researchers were able to identify a previously unknown bacterial species, which they named Subdoligranulum didolesgii.
The researchers postulated that the immune response in the gut to S. didolesgii might progress to a systemic immune response. To investigate this, they administered an oral dose of the bacterium to mice and monitored their immune and physical reactions. The mice developed antibodies and T cells that targeted their joints, resulting in visible joint swelling. Furthermore, the observed immunological changes in the mice extended from the gut mucosa to various sites throughout the body over time.
The combined findings suggest that certain individuals with RA may experience immune responses to S. didolesgii in the gut. This can lead to the production of antibodies and T cells that travel throughout the body and attack the joints, causing persistent inflammation.
- Chriswell ME, Lefferts AR, Clay MR, Hsu AR, Seifert J, Feser ML, Rims C, Bloom MS, Bemis EA, Liu S, Maerz MD, Frank DN, Demoruelle MK, Deane KD, James EA, Buckner JH, Robinson WH, Holers VM, Kuhn KA. Clonal IgA and IgG autoantibodies from individuals at risk for rheumatoid arthritis identify an arthritogenic strain of Subdoligranulum. Sci Transl Med. 2022 Oct 26;14(668):eabn5166. doi: 10.1126/scitranslmed.abn5166. Epub 2022 Oct 26. PMID: 36288282; PMCID: PMC9804515.