title: Increased complement activation in human type 1 diabetes pancreata.
abstract: OBJECTIVE
  Evidence supporting an association between complement (C) and type 1 diabetes (T1D) includes the identification of C-fixing islet cell autoantibodies in T1D sera and genetic associations with the major histocompatibility complex III C4 region on chromosome 6. Therefore, we investigated whether C activation was present in pancreata from those with or at increased risk (positive for T1D associated autoantibodies) for T1D.
  
  
  METHODS
  Immunohistochemical techniques were used to measure the C degradation product C4d in organ donor pancreata from patients with T1D and type 2 diabetes and autoantibody-positive and autoantibody-negative subjects.
  
  
  RESULTS
  Median C4d antigen density differed across the groups (P < 0.0001) and was highest in patients with T1D. C4d immunostaining localized to the blood vessel endothelium and extracellular matrix surrounding blood vessels and exocrine ducts. Receiver operating characteristic analysis resulted in 81.8% sensitivity and 94.4% specificity for C4d staining.
  
  
  CONCLUSIONS
  These data suggest that C activation is occurring within pancreata from patients with T1D and C4d may be a biomarker for T1D.
authors.affiliation: Corresponding author: Desmond Schatz, schatz@ufl.edu.
authors.forename: Patrick
authors.initials: P
authors.lastname: Rowe
authors.forename: Clive
authors.initials: C
authors.lastname: Wasserfall
authors.forename: Byron
authors.initials: B
authors.lastname: Croker
authors.forename: Martha
authors.initials: M
authors.lastname: Campbell-Thompson
authors.forename: Alberto
authors.initials: A
authors.lastname: Pugliese
authors.forename: Mark
authors.initials: M
authors.lastname: Atkinson
authors.forename: Desmond
authors.initials: D
authors.lastname: Schatz
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D002102:Cadaver; D002648:Child; D003167:Complement Activation; D003181:Complement C4 / Q000032:analysis*; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology; D005260:Female; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics; D008297:Male; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D003181:Complement C4
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