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