title: Heterogeneity and Lobularity of Pancreatic Pathology in Type 1 Diabetes during the Prediabetic Phase.
abstract: 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.
authors.affiliation: Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, California (TRC, JSS, NA, JZG, FA, SS, MGVH)
authors.forename: Teresa
authors.initials: T
authors.lastname: Rodriguez-Calvo
authors.affiliation: Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, California (TRC, JSS, NA, JZG, FA, SS, MGVH)|Department of Immunohematology & Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands (JSS)
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Suwandi
authors.affiliation: Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, California (TRC, JSS, NA, JZG, FA, SS, MGVH)
authors.forename: Natalie
authors.initials: N
authors.lastname: Amirian
authors.affiliation: Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, California (TRC, JSS, NA, JZG, FA, SS, MGVH)
authors.forename: Jose
authors.initials: J
authors.lastname: Zapardiel-Gonzalo
authors.affiliation: Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, California (TRC, JSS, NA, JZG, FA, SS, MGVH)
authors.forename: Florence
authors.initials: F
authors.lastname: Anquetil
authors.affiliation: Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, California (TRC, JSS, NA, JZG, FA, SS, MGVH)
authors.forename: Somayeh
authors.initials: S
authors.lastname: Sabouri
authors.affiliation: Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, California (TRC, JSS, NA, JZG, FA, SS, MGVH)|Novo Nordisk Diabetes Research & Development Center, Seattle, Washington (MGVH)
authors.forename: Matthias G
authors.initials: MG
authors.lastname: von Herrath
mesh_terms: D001323:Autoantibodies / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D008297:Male; D010179:Pancreas / Q000378:metabolism / Q000473:pathology*; D011236:Prediabetic State / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015395:Histocompatibility Antigens Class I
keywords: CD8 T cells; MHC-I; autoantibody positive; immunofluorescence; islet pathology; pancreatic islets; type 1 diabetes