Analysis of pancreas tissue in a child positive for islet cell antibodies

Diabetologia. 2008 Oct;51(10):1796-802. doi: 10.1007/s00125-008-1107-8. Epub 2008 Aug 12.


Aims/hypothesis: Type 1 diabetes is caused by an immune-mediated process, reflected by the appearance of autoantibodies against pancreatic islets in the peripheral circulation. Detection of multiple autoantibodies predicts the development of diabetes, while positivity for a single autoantibody is a poor prognostic marker. The present study assesses whether positivity for a single autoantibody correlates with pathological changes in the pancreas.

Methods: We studied post mortem pancreatic tissue of a child who repeatedly tested positive for islet cell antibodies (ICA) in serial measurements. Paraffin sections were stained with antibodies specific for insulin, glucagon, somatostatin, interferon alpha, CD3, CD68, cyclooxygenase-2 (COX-2), beta-2-microglobulin, coxsackie B and adenovirus receptor (CAR), natural killer and dendritic cells. Apoptosis was detected using Fas-specific antibody and TUNEL assay. Enterovirus was searched for using immunohistochemistry and in situ hybridisation, as well as enterovirus-specific RT-PCR from serum samples.

Results: The structure of the pancreas did not differ from normal. The number of beta cells was not reduced and no signs of insulitis were observed. Beta-2-microglobulin and CAR were strongly produced in the islets, but not in the exocrine pancreas. Enterovirus protein was detected selectively in the islets by two enterovirus-specific antibodies, but viral RNA was not found.

Conclusions/interpretation: These observations suggest that positivity for ICA alone, even when lasting for more than 1 year, is not associated with inflammatory changes in the islets. However, it is most likely that the pancreatic islets were infected by an enterovirus in this child.

Publication types

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

MeSH terms

  • Antibodies, Viral / analysis
  • Antigens, CD / analysis
  • Antigens, Differentiation, Myelomonocytic / analysis
  • Apoptosis
  • Autoantibodies / immunology*
  • CD3 Complex / analysis
  • Child
  • Cyclooxygenase 2 / analysis
  • Enterovirus / genetics
  • Enterovirus / immunology
  • Fatal Outcome
  • Glucagon / analysis
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Insulin / analysis
  • Interferon-alpha / analysis
  • Islets of Langerhans / cytology
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / metabolism
  • Pancreas / cytology
  • Pancreas / immunology*
  • Pancreas / metabolism
  • Receptors, Virus / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Somatostatin / analysis


  • Antibodies, Viral
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Autoantibodies
  • CD3 Complex
  • CD68 antigen, human
  • Insulin
  • Interferon-alpha
  • Receptors, Virus
  • adenovirus receptor
  • islet cell antibody
  • Somatostatin
  • Glucagon
  • Cyclooxygenase 2