Heterogeneity and Lobularity of Pancreatic Pathology in Type 1 Diabetes during the Prediabetic Phase

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 ag...

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Published in:The journal of histochemistry and cytochemistry Vol. 63; no. 8; p. 626
Main Authors: Rodriguez-Calvo, Teresa, Suwandi, Jessica S, Amirian, Natalie, Zapardiel-Gonzalo, Jose, Anquetil, Florence, Sabouri, Somayeh, von Herrath, Matthias G
Format: Journal Article
Language:English
Published: United States 01.08.2015
Subjects:
Autoantibodies - metabolism
Diabetes Mellitus, Type 1 - metabolism
Diabetes Mellitus, Type 1 - pathology
Histocompatibility Antigens Class I - biosynthesis
Histocompatibility Antigens Class I - metabolism
Humans
Male
Pancreas - metabolism
Pancreas - pathology
Prediabetic State - metabolism
Prediabetic State - pathology
Young Adult
type 1 diabetes
islet pathology
MHC-I
autoantibody positive
pancreatic islets
CD8 T cells
immunofluorescence
ISSN:1551-5044, 1551-5044
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Summary: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.
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ISSN:1551-5044
1551-5044
DOI:10.1369/0022155415576543