Kiel M Telesford1, Ulrike W Kaunzner2, Jai Perumal2, Susan A Gauthier2, Xian Wu2, Ivan Diaz2, Mason Kruse-Hoyer2, Casey Engel2, Melanie Marcille2, Timothy Vartanian1. 1. From the Brain and Mind Research Institute (K.M.T., T.V.), Weill Cornell Medicine; Department of Neurology (K.M.T., U.W.K., J.P., S.A.G., M.K.-H., C.E., M.M., T.V.), Weill Cornell Medicine; and Department of Healthcare Policy and Research (X.W., I.D.), Weill Cornell Medicine, New York. kit2003@med.cornell.edu tiv2002@med.cornell.edu. 2. From the Brain and Mind Research Institute (K.M.T., T.V.), Weill Cornell Medicine; Department of Neurology (K.M.T., U.W.K., J.P., S.A.G., M.K.-H., C.E., M.M., T.V.), Weill Cornell Medicine; and Department of Healthcare Policy and Research (X.W., I.D.), Weill Cornell Medicine, New York.
Abstract
OBJECTIVE: To determine the influence of self-reported Black African and Latin American identity on peripheral blood antibody-secreting cell (ASC) frequency in the context of relapsing-remitting MS. METHODS: In this cross-sectional study, we recruited 74 subjects with relapsing-remitting MS and 24 age-, and self-reported ethno-ancestral identity-matched healthy donors (HDs) to provide peripheral blood study samples. Subjects with MS were either off therapy at the time of study draw or on monthly natalizumab therapy infusions. Using flow cytometry, we assessed peripheral blood mononuclear cells for antibody-secreting B-cell subsets. RESULTS: When stratified by self-reported ethno-ancestry, we identified significantly elevated frequencies of circulating plasmablasts among individuals with MS identifying as Black African or Latin American relative to those of Caucasian ancestry. Ethno-ancestry-specific differences in ASC frequency were observed only among individuals with MS. By contrast, this differential was not observed among HDs. ASCs linked with poorer MS prognosis and active disease, including IgM+- and class-switched CD138+ subsets, were among those significantly increased. CONCLUSION: The enhanced peripheral blood plasmablast signature revealed among Black African or Latin American subjects with MS points to distinct underlying mechanisms associated with MS immunopathogenesis. This dysregulation may contribute to the disease disparity experienced by patient populations of Black African or Latin American ethno-ancestry.
OBJECTIVE: To determine the influence of self-reported Black African and Latin American identity on peripheral blood antibody-secreting cell (ASC) frequency in the context of relapsing-remitting MS. METHODS: In this cross-sectional study, we recruited 74 subjects with relapsing-remitting MS and 24 age-, and self-reported ethno-ancestral identity-matched healthy donors (HDs) to provide peripheral blood study samples. Subjects with MS were either off therapy at the time of study draw or on monthly natalizumab therapy infusions. Using flow cytometry, we assessed peripheral blood mononuclear cells for antibody-secreting B-cell subsets. RESULTS: When stratified by self-reported ethno-ancestry, we identified significantly elevated frequencies of circulating plasmablasts among individuals with MS identifying as Black African or Latin American relative to those of Caucasian ancestry. Ethno-ancestry-specific differences in ASC frequency were observed only among individuals with MS. By contrast, this differential was not observed among HDs. ASCs linked with poorer MS prognosis and active disease, including IgM+- and class-switched CD138+ subsets, were among those significantly increased. CONCLUSION: The enhanced peripheral blood plasmablast signature revealed among Black African or Latin American subjects with MS points to distinct underlying mechanisms associated with MS immunopathogenesis. This dysregulation may contribute to the disease disparity experienced by patient populations of Black African or Latin American ethno-ancestry.
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