{"doi":"10.1002/art.41927","title":"Defective Early B Cell Tolerance Checkpoints in Patients With Systemic Sclerosis Allow the Production of <scp>Self Antigen</scp>–Specific Clones","abstract":"OBJECTIVE: Early selection steps preventing autoreactive naive B cell production are often impaired in patients with autoimmune diseases, but central and peripheral B cell tolerance checkpoints have not been assessed in patients with systemic sclerosis (SSc). This study was undertaken to characterize early B cell tolerance checkpoints in patients with SSc. METHODS: CD27- new emigrant/transitional B cells and 190 CD19+CD21+CD10-IgM+CD27- mature naive B cells from 10 patients with SSc. RESULTS: Compared to serum from healthy donors, serum from patients with SSc displayed elevated proportions of polyreactive and antinuclear-reactive new emigrant/transitional B cells that recognize topoisomerase I, suggesting that defective central B cell tolerance contributes to the production of serum autoantibodies characteristic of the disease. Frequencies of autoreactive mature naive B cells were also significantly increased in SSc patients compared to healthy donors, thus indicating that a peripheral B cell tolerance checkpoint may be impaired in SSc. CONCLUSION: Defective counterselection of developing autoreactive naive B cells in SSc leads to the production of self antigen-specific B cells that may secrete autoantibodies and allow the formation of immune complexes, which promote fibrosis in SSc.","journal":"Arthritis & Rheumatology","year":2021,"id":176547,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9467,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":632201,"name":"Brennan Olson","orcid":"0000-0003-2803-5363","position":1,"is_corresponding":false},{"id":719800,"name":"Christopher May","orcid":null,"position":2,"is_corresponding":false},{"id":700766,"name":"Daniele Parisi","orcid":"0000-0002-2497-7487","position":3,"is_corresponding":false},{"id":719208,"name":"Christopher Massad","orcid":"0000-0002-4786-4880","position":4,"is_corresponding":false},{"id":56027,"name":"James E. Hansen","orcid":"0000-0002-2241-666X","position":5,"is_corresponding":false},{"id":634146,"name":"Changwan Ryu","orcid":"0000-0001-6211-4327","position":6,"is_corresponding":false},{"id":449354,"name":"Erica L. Herzog","orcid":"0000-0002-7508-8575","position":7,"is_corresponding":false},{"id":395328,"name":"Eric Meffre","orcid":"0000-0003-4326-0171","position":8,"is_corresponding":false},{"id":395327,"name":"Salomé Glauzy","orcid":"0009-0001-7508-9287","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T23:47:23.605867Z","pmid":"34279059","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":[]}