Author/Authors :
Pfleger، نويسنده , , C. and Kaas، نويسنده , , A. and Hansen، نويسنده , , L. and Alizadeh، نويسنده , , B. and Hougaard، نويسنده , , P. and Holl، نويسنده , , R. A. Kolb، نويسنده , , H. and Roep، نويسنده , , Jens Bo and Mortensen، نويسنده , , H.B. and Schloot، نويسنده , , N.C.، نويسنده ,
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 β-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 β-cell stress marker proinsulin but increased in remitters. CCL4 associated with decreased β-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.
Keywords :
Remission , Proinsulin , CCL5/RANTES , CCL3/MIP-1alpha , C-peptide , Disease progression , children , Type 1 Diabetes Mellitus , CCL4/MIP-1beta , inflammation
