{"doi":"10.3389/fimmu.2022.972127","title":"Distinct CD4+ T cell signature in ANA-positive young adult patients","abstract":"Failure of immune tolerance can lead to autoantibody production resulting in autoimmune diseases, a broad spectrum of organ-specific or systemic disorders. Immune tolerance mechanisms regulate autoreactive T and B cells, yet some lymphocytes escape and promote autoantibody production. CD4+ T cell dysregulation, characterized by decreased or impaired regulatory cells (Tregs) and/or accumulation of memory and effector T cells such as TH17, plays a crucial role in the pathogenesis of these diseases. Antinuclear antibody (ANAs) testing is used as a first step for the diagnosis of autoimmune disorders, although most ANA-positive individuals do not have nor will develop an autoimmune disease. Studying the differences of T cell compartment among healthy blood donors, ANA-negative patients and ANA-positive patients, in which loss of tolerance have not led to autoimmunity, may improve our understanding on how tolerance mechanisms fail. Herein, we report that ANA-positive patients exhibit a distinct distribution of T cell subsets: significantly reduced frequencies of recent thymic emigrants (RTE) and naïve T cells, and significantly increased frequencies of central memory T cells, TH2 and TH17 cells; modulations within the T cell compartment are most profound within the 18-40 year age range. Moreover, CD4+ T cells in ANA-positive patients are metabolically active, as determined by a significant increase in mTORC1 and mTORC2 signals, compared to ANA-negative patients and healthy blood donors. No significant impairment of Treg numbers or pro-inflammatory cytokine production was observed. These results identify a unique T cell signature associated with autoantibody production in the absence of autoimmune disease.","journal":"Frontiers in Immunology","year":2022,"id":268350,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9492,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":781232,"name":"Chiara Moriconi","orcid":"0000-0001-7942-2166","position":1,"is_corresponding":false},{"id":448418,"name":"Annie Qiu","orcid":null,"position":2,"is_corresponding":false},{"id":930016,"name":"Anabel Miller","orcid":"0000-0002-2692-1655","position":3,"is_corresponding":false},{"id":110272,"name":"Krystalyn E. Hudson","orcid":"0000-0001-5663-9290","position":4,"is_corresponding":false},{"id":229315,"name":"Flavia Dei Zotti","orcid":null,"position":0,"is_corresponding":true}],"reference_count":90,"raw_metadata":null,"created_at":"2026-07-19T00:27:10.233250Z","pmid":"36311777","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":[]}