title: Analysis of peri-islet CD45-positive leucocytic infiltrates in long-standing type 1 diabetic patients.
abstract: OBJECTIVE
  The role of peri-islet CD45-positive leucocytes, as one component of insulitis, in beta cell death during human type 1 diabetes remains unclear. We undertook a case study, comparing and quantifying leucocytes in the peri- and intra-islet areas in insulin-positive and -negative islets, to assess whether peri-islet leucocytes are pathogenic to beta cells during type 1 diabetes.
  
  
  METHODS
  Pancreatic sections from 12 diabetic patients (0.25-12 years of disease) and 13 non-diabetic individuals with and without autoantibodies were triple-immunostained for islet leucocytes, insulin and glucagon cells. Islets were graded for insulitis, enumerated and mapped for the spatial distribution of leucocytes in peri- and intra-islet areas in relation to insulin- and glucagon-immunopositive cells.
  
  
  RESULTS
  In the non-diabetic autoantibody-negative group, the percentage of islets with insulitis was either absent or <1% in five out of eight cases and ranged from 1.3% to 19.4% in three cases. In the five non-diabetic autoantibody-positive cases, it varied from 1.5% to 16.9%. In the diabetic group, it was <1% in one case and 1.1-26.9% in 11 cases, with insulitis being absent in 68% of insulin-positive islets. Peri-islet leucocytes were more numerous than intra-islet leucocytes in islets with insulin positivity. Increasing numbers of exocrine leucocytes in non-diabetic autoantibody-positive and diabetic donors were also present.
  
  
  CONCLUSIONS
  The prominence of peri-islet leucocytes in insulin-positive islets in most long-standing diabetic individuals suggests that they may be pathogenic to residual beta cells. Increasing numbers of leucocytes in the exocrine region may also participate in the pathogenesis of type 1 diabetes.
authors: Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand, s.reddy@auckland.ac.nz.
authors: Shiva
authors: S
authors: Reddy
authors: Nina
authors: N
authors: Zeng
authors: Hussam
authors: H
authors: Al-Diery
authors: Doran
authors: D
authors: Jung
authors: Clifton
authors: C
authors: Yeu
authors: Maximilian O
authors: MO
authors: Joret
authors: Mervyn J
authors: MJ
authors: Merrilees
authors: Fiona
authors: F
authors: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D055815:Young Adult
chemical_list: D017493:Leukocyte Common Antigens