Pathogenic Autoreactive T and B Cells Cross-React with Mimotopes Expressed by a Common Human Gut Commensal to Trigger Autoimmunity.
| Publication Type | Academic Article |
| Authors | Ruff W, Dehner C, Kim W, Pagovich O, Aguiar C, Yu A, Roth A, Vieira S, Kriegel C, Adeniyi O, Mulla M, Abrahams V, Kwok W, Nussinov R, Erkan D, Goodman A, Kriegel M |
| Journal | Cell Host Microbe |
| Volume | 26 |
| Issue | 1 |
| Pagination | 100-113.e8 |
| Date Published | 06/18/2019 |
| ISSN | 1934-6069 |
| Keywords | Antibodies, Bacterial, Antigens, Bacterial, Autoimmunity, B-Lymphocytes, Clostridiales, Cross Reactions, T-Lymphocytes |
| Abstract | Given the immense antigenic load present in the microbiome, we hypothesized that microbiota mimotopes can be a persistent trigger in human autoimmunity via cross-reactivity. Using antiphospholipid syndrome (APS) as a model, we demonstrate cross-reactivity between non-orthologous mimotopes expressed by a common human gut commensal, Roseburia intestinalis (R. int), and T and B cell autoepitopes in the APS autoantigen β2-glycoprotein I (β2GPI). Autoantigen-reactive CD4+ memory T cell clones and an APS-derived, pathogenic monoclonal antibody cross-reacted with R. int mimotopes. Core-sequence-dependent anti-R. int mimotope IgG titers were significantly elevated in APS patients and correlated with anti-β2GPI IgG autoantibodies. R. int immunization of mice induced β2GPI-specific lymphocytes and autoantibodies. Oral gavage of susceptible mice with R. int induced anti-human β2GPI autoantibodies and autoimmune pathologies. Together, these data support a role for non-orthologous commensal-host cross-reactivity in the development and persistence of autoimmunity in APS, which may apply more broadly to human autoimmune disease. |
| DOI | 10.1016/j.chom.2019.05.003 |
| PubMed ID | 31227334 |
| PubMed Central ID | PMC8194364 |