{"doi":"10.1101/2024.02.07.576204","title":"Systems Analysis of Immune Changes after B-cell Depletion in Autoimmune Multiple Sclerosis","abstract":"Abstract Multiple sclerosis (MS) is a complex genetically mediated autoimmune disease of the central nervous system where anti-CD20-mediated B cell depletion is remarkably effective in the treatment of early disease. While previous studies investigated the effect of B cell depletion on select immune cell subsets using flow cytometry-based methods, the therapeutic impact on patient immune landscape is unknown. In this study, we explored how a therapy-driven “ in vivo perturbation ” modulates the diverse immune landscape by measuring transcriptomic granularity with single-cell RNA sequencing (scRNAseq). We demonstrate that B cell depletion leads to cell type-specific changes in the abundance and function of CSF macrophages and peripheral blood monocytes. Specifically, a CSF-specific macrophage population with an anti-inflammatory transcriptomic signature and peripheral CD16 + monocytes increased in frequency post-B cell depletion. In addition, we observed increases in TNFα messenger RNA and protein in monocytes post-B cell depletion, consistent with the finding that anti-TNFα treatment exacerbates autoimmune activity in MS. In parallel, B cell depletion also induced changes in peripheral CD4 + T cell populations, including increases in the frequency of TIGIT + regulatory T cells and marked decreases in the frequency of myelin peptide loaded-tetramer binding CD4 + T cells. Collectively, this study provides an exhaustive transcriptomic map of immunological changes, revealing different mechanisms of action contributing to the high efficacy in B cell depletion treatment of MS.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":485403,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1327955,"name":"Jeonghyeon Moon","orcid":"0000-0002-5384-4077","position":1,"is_corresponding":false},{"id":1327956,"name":"Yoshiaki Yasumizu","orcid":"0000-0002-9872-4909","position":2,"is_corresponding":false},{"id":69461,"name":"Le Zhang","orcid":"0000-0002-4860-831X","position":3,"is_corresponding":false},{"id":1328416,"name":"Khadir Radassi","orcid":null,"position":4,"is_corresponding":false},{"id":1129327,"name":"Nicholas Buitrago-Pocasangre","orcid":"0000-0002-1333-4435","position":5,"is_corresponding":false},{"id":308941,"name":"M. 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