{"doi":"10.1126/scitranslmed.ade3614","title":"Measuring anti-islet autoimmunity in mouse and human by profiling peripheral blood antigen-specific CD4 T cells","abstract":"The endocrine pancreas is one of the most inaccessible organs of the human body. Its autoimmune attack leads to type 1 diabetes (T1D) in a genetically susceptible population and a lifelong need for exogenous insulin replacement. Monitoring disease progression by sampling peripheral blood would provide key insights into T1D immune-mediated mechanisms and potentially change preclinical diagnosis and the evaluation of therapeutic interventions. This effort has been limited to the measurement of circulating anti-islet antibodies, which despite a recognized diagnostic value, remain poorly predictive at the individual level for a fundamentally CD4 T cell-dependent disease. Here, peptide-major histocompatibility complex tetramers were used to profile blood anti-insulin CD4 T cells in mice and humans. While percentages of these were not directly informative, the state of activation of anti-insulin T cells measured by RNA and protein profiling was able to distinguish the absence of autoimmunity versus disease progression. Activated anti-insulin CD4 T cell were detected not only at time of diagnosis but also in patients with established disease and in some at-risk individuals. These results support the concept that antigen-specific CD4 T cells might be used to monitor autoimmunity in real time. This advance can inform our approach to T1D diagnosis and therapeutic interventions in the preclinical phase of anti-islet autoimmunity.","journal":"Science Translational Medicine","year":2023,"id":341305,"datarank":0.551766022183366,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.13587771384739875,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.13587771384739875,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":10,"citers_with_citation_signal":7,"citers_with_endowment":7,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":true,"deposit_databanks":{"Dryad":["10.5061/dryad.79cnp5j1h"]},"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":1076793,"name":"Xuqian Tan","orcid":"0000-0001-6044-8876","position":1,"is_corresponding":false},{"id":1077322,"name":"Josh Boyer","orcid":null,"position":2,"is_corresponding":false},{"id":971179,"name":"Don Clarke","orcid":"0000-0003-1917-1566","position":3,"is_corresponding":false},{"id":1076794,"name":"Anne Costanzo","orcid":"0000-0003-1934-5319","position":4,"is_corresponding":false},{"id":839589,"name":"Brian T. Abe","orcid":"0000-0002-1262-5556","position":5,"is_corresponding":false},{"id":1076795,"name":"Lisa Kain","orcid":"0000-0001-5873-8647","position":6,"is_corresponding":false},{"id":1076796,"name":"Marie Holt","orcid":"0000-0003-0763-4535","position":7,"is_corresponding":false},{"id":1077323,"name":"ADRIENNE ARMSTRONG","orcid":null,"position":8,"is_corresponding":false},{"id":776130,"name":"Marynette Rihanek","orcid":"0009-0003-2274-4318","position":9,"is_corresponding":false},{"id":37901,"name":"Andrew I. Su","orcid":"0000-0002-9859-4104","position":10,"is_corresponding":false},{"id":271012,"name":"Cate Speake","orcid":"0000-0003-1480-4272","position":11,"is_corresponding":false},{"id":336608,"name":"Peter A. Gottlieb","orcid":"0000-0002-7601-8536","position":12,"is_corresponding":false},{"id":1076797,"name":"Michael Gottschalk","orcid":"0000-0002-5214-9929","position":13,"is_corresponding":false},{"id":237704,"name":"Jeremy Pettus","orcid":"0000-0002-5999-0091","position":14,"is_corresponding":false},{"id":91049,"name":"Luc Teyton","orcid":"0000-0002-4049-1583","position":15,"is_corresponding":false},{"id":987320,"name":"Siddhartha Sharma","orcid":"0000-0001-8597-7547","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T01:11:03.393978Z","pmid":"37406136","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":[]}