{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:29:26Z","timestamp":1790479766178,"version":"4.1.0"},"reference-count":38,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2015,7,27]],"date-time":"2015-07-27T00:00:00Z","timestamp":1437955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Histochem Cytochem."],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:p>Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing beta cells are destroyed in the islets of Langerhans. One of its main pathological manifestations is the hyper-expression of Major Histocompatibility Complex I (MHC-I) by beta cells, which was first described over 3 decades ago yet its cause remains unknown. It might not only be a sign of beta cell dysfunction but could also render the cells susceptible to autoimmune destruction; for example, by islet-infiltrating CD8 T cells. In this report, we studied pancreas tissue from a 22-year-old non-diabetic male cadaveric organ donor who had been at high risk of developing T1D, in which autoantibodies against GAD and IA-2 were detected. Pancreas sections were analyzed for signs of inflammation. Multiple insulin-containing islets were identified, which hyper-expressed MHC-I. However, islet density and MHC-I expression exhibited a highly lobular and heterogeneous pattern even within the same section. In addition, many islets with high expression of MHC-I presented higher levels of CD8 T cell infiltration than normal islets. These results demonstrate the heterogeneity of human pathology that occurs early during the pre-diabetic, autoantibody positive phase, and should contribute to the understanding of human T1D.<\/jats:p>","DOI":"10.1369\/0022155415576543","type":"journal-article","created":{"date-parts":[[2015,7,27]],"date-time":"2015-07-27T12:38:13Z","timestamp":1438000693000},"page":"626-636","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":71,"title":["Heterogeneity and Lobularity of Pancreatic Pathology in Type 1 Diabetes during the Prediabetic Phase"],"prefix":"10.1369","volume":"63","author":[{"given":"Teresa","family":"Rodriguez-Calvo","sequence":"first","affiliation":[{"name":"Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, California (TRC, JSS, NA, JZG, FA, SS, MGVH)"},{"name":"Department of Immunohematology & Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands 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