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  • 1
    Online Resource
    Online Resource
    Wiley ; 2022
    In:  Annals of Clinical and Translational Neurology Vol. 9, No. 7 ( 2022-07), p. 962-976
    In: Annals of Clinical and Translational Neurology, Wiley, Vol. 9, No. 7 ( 2022-07), p. 962-976
    Abstract: Multiple sclerosis (MS) is a neuroinflammatory disease where immune cells cross the blood–brain barrier (BBB) into the central nervous system (CNS). What predisposes these immune cells to cross the BBB is still unknown. Here, we examine the possibility that genomic rearrangements could predisposespecific immune cells in the peripheral blood to cross the BBB and form sub‐populations of cells involved in the inflammatory process in the CNS. Methods We compared copy number variations in paired peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid (CSF) cells from MS patients. Thereafter, using next generation sequencing, we studied the T‐cell receptor beta (TRB) locus rearrangements and profiled the αβ T cell repertoire in peripheral CD4 + and CD8 + T cells and in the CSF. Results We identified deletions in the T‐cell receptor alpha/delta (TRA/D), gamma (TRG), and TRB loci in CSF cells compared to PBMCs. Further characterization revealed diversity of the TRB locus which was used to describe the character and clonal expansion of T cells in the CNS. T‐cell repertoire profiling from either side of the BBB concluded that the most frequent clones in the CSF samples are unique to an individual. Furthermore, we observed a difference in the proportion of expanded T‐cell clones when comparing samples from MS patients in relapse and remission with opposite trends in CSF and peripheral blood. Interpretation This study provides a characterization of the T cells in the CSF and might indicate a role of expanded clones in MS pathogenicity.
    Type of Medium: Online Resource
    ISSN: 2328-9503 , 2328-9503
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2740696-9
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  • 2
    In: European Journal of Neurology, Wiley, Vol. 29, No. 11 ( 2022-11), p. 3317-3328
    Abstract: Recent findings document a blunted humoral response to SARS‐CoV‐2 vaccination in patients on anti‐CD20 treatment. Although most patients develop a cellular response, it is still important to identify predictors of seroconversion to optimize vaccine responses. Methods We determined antibody responses after SARS‐CoV‐2 vaccination in a real‐world cohort of multiple sclerosis patients ( n  = 94) treated with anti‐CD20, mainly rituximab, with variable treatment duration (median = 2.9, range = 0.4–9.6 years) and time from last anti‐CD20 infusion to vaccination (median = 190, range = 60–1032 days). Results We find that presence of B cells and/or rituximab in blood predict seroconversion better than time since last infusion. Using multiple logistic regression, presence of 〉 0.5% B cells increased probability of seroconversion with an odds ratio (OR) of 5.0 (95% confidence interval [CI] = 1.0–28.1, p  = 0.055), whereas the corresponding OR for ≥6 months since last infusion was 1.45 (95% CI = 0.20–10.15, p  = 0.705). In contrast, detectable rituximab levels were negatively associated with seroconversion (OR = 0.05, 95% CI = 0.002–0.392, p  = 0.012). Furthermore, naïve and memory IgG + B cells correlated with antibody levels. Although retreatment with rituximab at 4 weeks or more after booster depleted spike‐specific B cells, it did not noticeably affect the rate of decline in antibody titers. Interferon‐γ and/or interleukin‐13 T‐cell responses to the spike S1 domain were observed in most patients, but with no correlation to spike antibody levels. Conclusions These findings are relevant for providing individualized guidance to patients and planning of vaccination schemes, in turn optimizing benefit–risk with anti‐CD20.
    Type of Medium: Online Resource
    ISSN: 1351-5101 , 1468-1331
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2020241-6
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