anti-Human IgA, Mouse monoclonal to Human IgA, Isotype IgG1, Host Mouse productsSearch results for: anti-Human IgA, Mouse monoclonal to Human IgA, Isotype IgG1, Host Mouse
#31227334 
2019/06/18
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Pathogenic Autoreactive T and B Cells Cross-React with Mimotopes Expressed by a Common Human Gut Commensal to Trigger Autoimmunity.
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 β-glycoprotein I (βGPI). 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-βGPI IgG autoantibodies. R. int immunization of mice induced βGPI-specific lymphocytes and autoantibodies. Oral gavage of susceptible mice with R. int induced anti-human βGPI 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.William E Ruff, Carina Dehner, Woo J Kim, Odelya Pagovich, Cassyanne L Aguiar, Andrew T Yu, Alexander S Roth, Silvio Manfredo Vieira, Christina Kriegel, Olamide Adeniyi, Melissa J Mulla, Vikki M Abrahams, William W Kwok, Ruth Nussinov, Doruk Erkan, Andrew L Goodman, Martin A Kriegel
