The immunobiology of apotransferrin in type 1 diabetes

Clin Exp Immunol. 2012 Sep;169(3):244-52. doi: 10.1111/j.1365-2249.2012.04619.x.

Abstract

The transferrin (Tf) family of iron binding proteins includes important endogenous modulators of the immune function that may modulate autoimmune diseases. To define more clearly the role of apotransferrin (apoTf) in type 1 diabetes we determined the impact of this protein on type 1 diabetes as investigated in islet cells, animal models and patient sera. First, we demonstrated that recombinant apoTf counteracts the cytokine-induced death of murine pancreatic islet cells. Secondly, human apoTf administration favourably influences the course of type 1 diabetes in animal models, resulting in protection against disease development that was associated with reduction of insulitis and reduced levels of proinflammatory cytokines. Finally, we confirmed that patients with newly diagnosed type 1 diabetes manifest significantly lower apoTf serum levels compared to healthy controls and patients with long-lasting disease. In conclusion, our data suggest the apoTf pivotal role in the perpetuation of type 1 diabetes pathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Apoproteins / blood
  • Apoproteins / chemistry
  • Apoproteins / immunology*
  • Cell Line, Tumor / drug effects
  • Cytokines / metabolism
  • Cytokines / pharmacology
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / prevention & control
  • Disease Progression
  • Female
  • Humans
  • Insulinoma / pathology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / immunology
  • Islets of Langerhans / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Pancreatitis / immunology
  • Pancreatitis / prevention & control
  • Rats
  • Rats, Inbred BB
  • Recombinant Proteins / pharmacology
  • T-Lymphocyte Subsets / immunology
  • Transferrin / chemistry
  • Transferrin / immunology*
  • Young Adult

Substances

  • Apoproteins
  • Cytokines
  • Recombinant Proteins
  • Transferrin
  • apotransferrin