Increased complement activation in human type 1 diabetes pancreata

Patrick Rowe, Clive Wasserfall, Byron Croker, Martha Campbell-Thompson, Alberto Pugliese, Mark Atkinson, Desmond Schatz

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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. Research Design and Methods - Immunohistochemical techniques were used to measure the C degradation product C4d in organ donor pancreata frompatients 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.

Original languageEnglish
Pages (from-to)3815-3817
Number of pages3
JournalDiabetes Care
Volume36
Issue number11
DOIs
StatePublished - Nov 1 2013

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Rowe, P., Wasserfall, C., Croker, B., Campbell-Thompson, M., Pugliese, A., Atkinson, M., & Schatz, D. (2013). Increased complement activation in human type 1 diabetes pancreata. Diabetes Care, 36(11), 3815-3817. https://doi.org/10.2337/dc13-0203