A Histological Study of Fulminant Type 1 Diabetes Mellitus Related to Human Cytomegalovirus Reactivation

J Clin Endocrinol Metab. 2017 Jul 1;102(7):2394-2400. doi: 10.1210/jc.2016-4029.

Abstract

Context: Fulminant type 1 diabetes mellitus (T1DM) is thought to be partly caused by virus infection.

Objective: This study investigated the mechanism of β cell destruction in fulminant T1DM after drug-induced hypersensitivity syndrome (DIHS).

Methods: We determined the localization of human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6), and Epstein-Barr virus (EBV) and the expression of interferon regulatory factor 3 (IRF3) and viral receptors of Z-DNA binding protein 1 (ZBP1) and retinoic acid-inducible gene I (RIG-I), together with inflammatory cells, by immunohistochemistry of the autopsy pancreas of a patient with fulminant T1DM with DIHS and in seven subjects with normal glucose tolerance who underwent pancreatectomy.

Results: HCMV-positive cells were detected in islets and exocrine areas in the patient with fulminant T1DM. Greater numbers of macrophages and CD4+ and CD8+ T lymphocytes had infiltrated into HCMV-positive islets than into HCMV-negative islets, and 52.6% of HCMV-positive cells were also positive for IRF3. α Cells expressed IRF3, ZBP1, or RIG-I. No HCMV-positive cells were detected in the control subjects. HHV-6-positive, but not EBV-positive, cells were present in the patient and the control subjects.

Conclusions: These findings indicate that the immunoresponse caused by HCMV infection was associated with β cell injury.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biopsy, Needle
  • Case-Control Studies
  • Cells, Cultured
  • Cytomegalovirus / pathogenicity*
  • Cytomegalovirus Infections / physiopathology*
  • DNA-Binding Proteins / metabolism
  • Diabetes Mellitus, Type 1 / pathology*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Humans
  • Immunohistochemistry
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / virology
  • Interferon Regulatory Factor-3 / metabolism*
  • Male
  • Reference Values
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Virus Activation*

Substances

  • DNA-Binding Proteins
  • Interferon Regulatory Factor-3
  • ZBP1 protein, human