Newly Discovered Gut Microbe Could Be a Trigger For Rheumatoid Arthritis!

 | Post date: 2023/01/17 | 
Rheumatoid arthritis affects millions worldwide and often leaves patients debilitated with chronic pain and joint inflammation. Scientists have long struggled to figure out the core causes of the condition. Now, research involving mice and a small group of patients has connected the early stages of rheumatoid arthritis to a newly discovered species of bacteria found in the gut microbiome — the vast community of microbes that assist digestion and influence human health. The new study, published in the October 26 issue of Science Translational Medicine, revealed that this bacterial species could trigger the formation of autoantibodies, or antibodies that target the body's own tissues. 
The mucosal origins hypothesis of rheumatoid arthritis (RA) proposes a central role for mucosal immune responses in the initiation or perpetuation of the systemic autoimmunity that occurs with disease. However, the connection between the mucosa and systemic autoimmunity in RA remains unclear. Using dual immunoglobulin A (IgA) and IgG family plasmablast–derived monoclonal autoantibodies obtained from peripheral blood of individuals at risk for RA, they identified cross-reactivity between RA-relevant autoantigens and bacterial taxa in the closely related families Lachnospiraceae and Ruminococcaceae. After generating bacterial isolates within the Lachnospiraceae/Ruminococcaceae genus Subdoligranulum from the feces of an individual, they confirmed monoclonal antibody binding and CD4+ T cell activation in individuals with RA compared to control individuals. In addition, when Subdoligranulum isolate 7 but not isolate 1 colonized germ-free mice, it stimulated TH17 cell expansion, serum RA–relevant IgG autoantibodies, and joint swelling reminiscent of early RA, with histopathology characterized by antibody deposition and complement activation. Systemic immune responses were likely due to mucosal invasion along with the generation of colon-isolated lymphoid follicles driving increased fecal and serum IgA by isolate 7, because B and CD4+ T cell depletion not only halted intestinal immune responses but also eliminated detectable clinical disease. In aggregate, these findings demonstrate a mechanism of RA pathogenesis through which a specific intestinal strain of bacteria can drive systemic autoantibody generation and joint-centered antibody deposition and immune activation.
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