Expression of human leukocyte antigen class I in endocrine and exocrine pancreatic tissue at onset of type 1 diabetes

Am J Pathol. 2015 Jan;185(1):129-38. doi: 10.1016/j.ajpath.2014.09.004.

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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / metabolism*
  • Genes, MHC Class I*
  • Humans
  • Interferons / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Islets of Langerhans / metabolism*
  • Middle Aged
  • Pancreas, Exocrine / metabolism*
  • Transcription Factors / metabolism
  • Transcriptome
  • Young Adult

Substances

  • Intracellular Signaling Peptides and Proteins
  • NLRC5 protein, human
  • Transcription Factors
  • Interferons