title: Expression of human leukocyte antigen class I in endocrine and exocrine pancreatic tissue at onset of type 1 diabetes.
abstract: The cause of type 1 diabetes remains unknown. To dissect the link between hyperexpression of human leukocyte antigen (HLA) class I on the islet cells, we examined its expression in subjects with recent-onset type 1 diabetes. IHC showed seemingly pronounced hyperexpression in subjects with recent-onset type 1 diabetes, as well as in some nondiabetic subjects. In all subjects, HLA class I expression on exocrine tissue was low. However, no difference in the level of HLA class I expression was found between islet and exocrine tissue using Western blot, flow cytometry, real-time quantitative PCR, or RNA sequencing analyses. Also, the level of HLA class I expression on the messenger level was not increased in islets from subjects with recent-onset type 1 diabetes compared with that in nondiabetic subjects. Consistently, the HLA class I specific enhanceosome (NLRC5) and related transcription factors, as well as interferons, were not enhanced in islets from recent-onset type 1 diabetic subjects. In conclusion, a discrepancy in HLA class I expression in islets assessed by IHC was observed compared with that using quantitative techniques showing similar expression of HLA class I in islets and exocrine tissue in subjects with recent-onset type 1 diabetes, nor could any differences be found between type 1 diabetic and nondiabetic subjects. Results presented provide important clues for a better understanding on how this complex disease develops.
authors.affiliation: Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Oskar
authors.initials: O
authors.lastname: Skog
authors.forename: Stella
authors.initials: S
authors.lastname: Korsgren
authors.forename: Anna
authors.initials: A
authors.lastname: Wiberg
authors.forename: Angelika
authors.initials: A
authors.lastname: Danielsson
authors.forename: Bjørn
authors.initials: B
authors.lastname: Edwin
authors.forename: Trond
authors.initials: T
authors.lastname: Buanes
authors.forename: Lars
authors.initials: L
authors.lastname: Krogvold
authors.forename: Olle
authors.initials: O
authors.lastname: Korsgren
authors.forename: Knut
authors.initials: K
authors.lastname: Dahl-Jørgensen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000378:metabolism*; D005805:Genes, MHC Class I; D006801:Humans; D007372:Interferons / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D008875:Middle Aged; D046790:Pancreas, Exocrine / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C548042:NLRC5 protein, human; D014157:Transcription Factors; D007372:Interferons