{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:24:05Z","timestamp":1787747045748,"version":"build-2784847793"},"reference-count":104,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunological Reviews"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Type 1 diabetes (T1D) is characterized by T cell\u2010mediated destruction of insulin producing pancreatic \u03b2 cells. However, stressed \u03b2 cells are increasingly recognized as active contributors to disease pathogenesis rather than passive targets of immune attack. In this context, oxidative stress in \u03b2 cells may promote oxidative post\u2010translational modifications (oxPTMs) of insulin, generating modified insulin forms that have emerged as potential drivers of neoantigen formation and autoimmune responses. Due to their exceptionally high insulin biosynthetic load, limited antioxidant defenses, and susceptibility to endoplasmic reticulum and mitochondrial stress, \u03b2 cells operate in an environment permissive to oxidative protein modification. Multiple studies have demonstrated that insulin is susceptible to several oxidative and nonenzymatic modifications, including oxidation, chlorination, nitration, and glycation, generating structurally distinct proteoforms with altered biological and immunological properties. Importantly, oxidatively modified insulin species (oxPTM\u2010insulin) are recognized by both autoantibodies and autoreactive T cells in individuals with T1D, supporting their role as neoantigens. In this review, we discuss the mechanisms leading to oxPTM\u2010insulin generation, summarize the biochemical and immunological evidence supporting their relevance in T1D, and examine the methodological challenges and controversies surrounding their identification. Finally, we explore the potential of oxPTM\u2010insulin as a biomarker and therapeutic target in T1D.<\/jats:p>","DOI":"10.1111\/imr.70159","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T06:25:34Z","timestamp":1786083934000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oxidative Post\u2010Translational Modifications of Insulin in Type 1 Diabetes Autoimmunity"],"prefix":"10.1111","volume":"341","author":[{"given":"Chiara","family":"Vinci","sequence":"first","affiliation":[{"name":"Center for Diabetes Research Universit\u00e9 Libre de Bruxelles  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Franzese","sequence":"additional","affiliation":[{"name":"Department for the Promotion of Human Science and Quality of Life San Raffaele Open University  Rome Italy"},{"name":"Universit\u00e0 Campus Bio\u2010Medico di Roma  Rome 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