ObjectiveTo develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment.MethodsTo illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks.ResultsAs of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female.ConclusionsCollectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD.

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MSWS-12 measurement error depends on walking ability, but could be lowered by improving or replacing items with low information or DIF. The e-MSWS-12 includes IRT-based scoring, error checking, and an estimated T25FW derived from MSWS-12 responses. It is available at https://ms-irt.shinyapps.io/e-MSWS-12 .

ObjectiveTo 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.MethodsIn 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.ResultsWhen 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.ConclusionThe 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.