The Antibody‐Microbiota Interface in Autoimmune Diseases

The human intestine harbors a dense community of commensal microbes that strongly shape humoral immune responses. While secretory immunoglobulin A (sIgA) has long been recognized as a key regulator of microbiota compartmentalization and intestinal homeostasis, recent studies have also highlighted important roles for secretory IgM and systemic IgG in host-microbiota interactions. In this review, we examine critical aspects of the antibody-microbiota interface, first showing the extent to which microbiota and factors influencing microbiota ecosystem such as diet shape sIgA repertoire and binding capacity. We further integrate insights from both murine and human studies to provide a comprehensive overview of how antibody-microbiota interactions are altered in autoimmune diseases and contribute both to the identification of microbial drivers of disease and to the development of new therapeutic approaches. It is noteworthy that myasthenia gravis (MG) patients have a unique microbial signature, different from other autoimmune diseases, suggesting that yet-to-be-identified gut bacteria might specifically drive the host's immune response toward MG. Finally, we discuss the mechanisms through which the microbiota may contribute to the initiation or perpetuation of dysregulated immune responses underlying autoimmunity. Given the presence of IgA autoantibodies in MG patients and the broad homology between the acetylcholine receptor and the microbial proteome, molecular mimicry and epitope spreading should be investigated as potential triggering mechanisms.