title: Analysis of pancreas tissue in a child positive for islet cell antibodies.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Virology, Medical School, University of Tampere, Biokatu 10, Tampere, Finland. maarit.oikarinen@uta.fi
authors.forename: M
authors.initials: M
authors.lastname: Oikarinen
authors.forename: S
authors.initials: S
authors.lastname: Tauriainen
authors.forename: T
authors.initials: T
authors.lastname: Honkanen
authors.forename: K
authors.initials: K
authors.lastname: Vuori
authors.forename: P
authors.initials: P
authors.lastname: Karhunen
authors.forename: C
authors.initials: C
authors.lastname: Vasama-Nolvi
authors.forename: S
authors.initials: S
authors.lastname: Oikarinen
authors.forename: C
authors.initials: C
authors.lastname: Verbeke
authors.forename: G E
authors.initials: GE
authors.lastname: Blair
authors.forename: I
authors.initials: I
authors.lastname: Rantala
authors.forename: J
authors.initials: J
authors.lastname: Ilonen
authors.forename: O
authors.initials: O
authors.lastname: Simell
authors.forename: M
authors.initials: M
authors.lastname: Knip
authors.forename: H
authors.initials: H
authors.lastname: Hyöty
mesh_terms: D000914:Antibodies, Viral / Q000032:analysis; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D017209:Apoptosis; D001323:Autoantibodies / Q000276:immunology*; D017252:CD3 Complex / Q000032:analysis; D002648:Child; D051546:Cyclooxygenase 2 / Q000032:analysis; D004770:Enterovirus / Q000235:genetics / Q000276:immunology; D017809:Fatal Outcome; D005934:Glucagon / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000032:analysis; D016898:Interferon-alpha / Q000032:analysis; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D011991:Receptors, Virus / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000032:analysis; D000097382:CD68 Molecule
chemical_list: D000914:Antibodies, Viral; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001323:Autoantibodies; D017252:CD3 Complex; D051546:Cyclooxygenase 2; D005934:Glucagon; D007328:Insulin; D016898:Interferon-alpha; D011991:Receptors, Virus; D013004:Somatostatin; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C085301:adenovirus receptor; C024211:islet cell antibody