Relation of circulating concentrations of chemokine receptor CCR5 ligands to C-peptide, proinsulin and HbA1c and disease progression in type 1 diabetes

Clin Immunol. 2008 Jul;128(1):57-65. doi: 10.1016/j.clim.2008.03.458. Epub 2008 Apr 22.

Abstract

Th1 related chemokines CCL3 and CCL5 and Th2 related CCL4 as ligands of the receptor CCR5 contribute to disease development in animal models of type 1 diabetes. In humans, no data are available addressing the role of these chemokines regarding disease progression and remission. We investigated longitudinally circulating concentrations of CCR5 ligands of 256 newly diagnosed patients with type 1 diabetes. CCR5 ligands were differentially associated with beta-cell function and clinical remission. CCL5 was decreased in remitters and positively associated with HbA1c suggestive of a Th1 associated progression of the disease. Likewise, CCL3 was negatively related to C-peptide and positively associated with the beta-cell stress marker proinsulin but increased in remitters. CCL4 associated with decreased beta-cell stress shown by negative association with proinsulin. Blockage of chemokines or antagonism of CCR5 by therapeutic agents such as maraviroc may provide a new therapeutic target to ameliorate disease progression in type 1 diabetes.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers / blood
  • C-Peptide / blood*
  • Chemokine CCL3 / blood
  • Chemokine CCL4 / blood
  • Chemokine CCL5 / blood
  • Chemokines / blood*
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glycated Hemoglobin / analysis*
  • Humans
  • Infant
  • Male
  • Proinsulin / blood*
  • Receptors, CCR5 / blood*

Substances

  • Biomarkers
  • C-Peptide
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokines
  • Glycated Hemoglobin A
  • Receptors, CCR5
  • hemoglobin A1c protein, human
  • Proinsulin