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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\u2013dependent disease. Here, peptide\u2013major 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.<\/jats:p>","DOI":"10.1126\/scitranslmed.ade3614","type":"journal-article","created":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T17:58:13Z","timestamp":1688579893000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":18,"title":["Measuring anti-islet autoimmunity in mouse and human by profiling peripheral blood antigen-specific CD4 T cells"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8597-7547","authenticated-orcid":true,"given":"Siddhartha","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, CA 92037, 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