{"doi":"10.1172/jci185217","title":"Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis","abstract":"Rheumatoid arthritis (RA) is a systemic autoimmune disease currently with no universally highly effective prevention strategies. Identifying pathogenic immune phenotypes in at-risk populations prior to clinical onset is crucial to establishing effective prevention strategies. Here, we applied multimodal single-cell technologies (mass cytometry and CITE-Seq) to characterize the immunophenotypes in blood from at-risk individuals (ARIs) identified through the presence of serum antibodies against citrullinated protein antigens (ACPAs) and/or first-degree relative (FDR) status, as compared with patients with established RA and people in a healthy control group. We identified significant cell expansions in ARIs compared with controls, including CCR2+CD4+ T cells, T peripheral helper (Tph) cells, type 1 T helper cells, and CXCR5+CD8+ T cells. We also found that CD15+ classical monocytes were specifically expanded in ACPA-negative FDRs, and an activated PAX5lo naive B cell population was expanded in ACPA-positive FDRs. Further, we uncovered the molecular phenotype of the CCR2+CD4+ T cells, expressing high levels of Th17- and Th22-related signature transcripts including CCR6, IL23R, KLRB1, CD96, and IL22. Our integrated study provides a promising approach to identify targets to improve prevention strategy development for RA.","journal":"Journal of Clinical Investigation","year":2025,"id":509545,"datarank":0.7167226432768354,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"self_citation_contribution":0.519860385419959,"citation_network_contribution":0.19686225785687636,"self_endowment_contribution":0.519860385419959,"citer_contribution":0.19686225785687636,"corpus_percentile":null,"corpus_rank":null,"citation_count":31,"citer_count":23,"citers_with_citation_signal":9,"citers_with_endowment":9,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":257106,"name":"Joshua Keegan","orcid":null,"position":1,"is_corresponding":false},{"id":720260,"name":"Alec Griffith","orcid":"0000-0002-4289-3017","position":2,"is_corresponding":false},{"id":495662,"name":"Tusharkanti Ghosh","orcid":"0000-0002-7537-6374","position":3,"is_corresponding":false},{"id":1149105,"name":"Alice Horisberger","orcid":"0000-0002-3732-8662","position":4,"is_corresponding":false},{"id":647903,"name":"Kaitlyn Howard","orcid":"0000-0002-9398-6176","position":5,"is_corresponding":false},{"id":1364435,"name":"John F. 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