{"doi":"10.1101/2023.02.26.23286433","title":"An EBV-associated atypical B cell signature in clinically isolated syndrome is implicated in progression of multiple sclerosis","abstract":"ABSTRACT Expansion and pathogenicity of CD19 + /CD20 + /CD11c + /T-bet + atypical B cells (ABCs) are hallmarks of numerous autoimmune disorders and chronic infections. In many such cases Epstein-Barr virus (EBV) is another associated or etiologic factor, though EBV involvement in these diseases remains poorly understood. Notably, the expansion of pro-inflammatory ABCs and a putative causal role for EBV have been identified independently in multiple sclerosis (MS). A common precipitating event in MS onset is Clinically Isolated Syndrome (CIS), a neuroinflammatory demyelinating condition of which 60-80% of cases progress to relapsing-remitting MS (RRMS). Here we report single-cell gene and surface protein expression (scRNA/CITE-seq) in peripheral B cells collected longitudinally from patients with CIS during the Immune Tolerance Network STAyCIS Trial. We focus on the transcriptomic signatures of ABCs from this cohort, publicly available scRNA-seq datasets from six other autoimmune and chronic infectious diseases, and in vitro EBV infection. Conservation of an expanded ABC expression profile across diseases establishes ABC dysregulation as a feature of CIS. Critically, we also observed transcriptomic features that distinguished CIS and de novo EBV-infected ABCs from those found in healthy controls and other disease contexts. Outcome stratification of CIS samples revealed a rare yet distinctive pro-inflammatory ABC subset that was significantly underrepresented in long-term non-progressor (LTNP) versus cases with RRMS activity (∼5-fold difference). Collectively, this study provides evidence for altered ABC regulation – possibly arising from niche-specific responses to EBV infection – preceding MS onset. SUMMARY Single-cell transcriptomics establishes an EBV-associated signature in T-bet + atypical B cells in CIS and a pro-inflammatory phenotype underrepresented in patients with no disease progression.","journal":"medRxiv","year":2023,"id":391701,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9482,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1164916,"name":"Ellora Haukenfrers","orcid":null,"position":1,"is_corresponding":false},{"id":229144,"name":"Vaibhav Jain","orcid":"0000-0003-2394-3426","position":2,"is_corresponding":false},{"id":997222,"name":"Karen Abramson","orcid":"0000-0002-3504-5933","position":3,"is_corresponding":false},{"id":59322,"name":"Emily Hocke","orcid":"0000-0002-0976-5814","position":4,"is_corresponding":false},{"id":927813,"name":"Laura A. Cooney","orcid":"0000-0001-7307-2548","position":5,"is_corresponding":false},{"id":256536,"name":"Kristina M. Harris","orcid":"0000-0002-6957-514X","position":6,"is_corresponding":false},{"id":246282,"name":"Scott S. Zamvil","orcid":"0000-0003-2720-9915","position":7,"is_corresponding":false},{"id":59323,"name":"Simon G. Gregory","orcid":"0000-0002-7805-1743","position":8,"is_corresponding":false},{"id":395715,"name":"Micah A. Luftig","orcid":"0000-0002-2964-1907","position":9,"is_corresponding":false},{"id":577327,"name":"Elliott D. SoRelle","orcid":"0000-0002-3362-1028","position":0,"is_corresponding":true}],"reference_count":136,"raw_metadata":null,"created_at":"2026-07-19T01:18:47.408273Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}