Relation of circulating concentrations of chemokine receptor CCR5 ligands to C-peptide, proinsulin and HbA1c and disease progression in type 1 diabetes
chemokines; Ccl3/Mip-1alpha; Ccl5/Rantes; Ccl4/Mip-1beta; Th2; type 1 diabetes mellitus; proinsulin; c-peptide; inflammation; disease progression; remission; children
Abstract :
[en] 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.
Disciplines :
Human health sciences: Multidisciplinary, general & others
Author, co-author :
Pfleger, C.
Kaas, A.
Hansen, L.
Alizadeh, B.
Hougaard, P.
Holl, R.
Holb, H.
Roep, B.O.
Mortensen, H.B.
Schloot, N.C.
Other collaborator :
De Beaufort, Carine ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
External co-authors :
yes
Language :
English
Title :
Relation of circulating concentrations of chemokine receptor CCR5 ligands to C-peptide, proinsulin and HbA1c and disease progression in type 1 diabetes
Publication date :
July 2008
Journal title :
Clinical Immunology
ISSN :
1521-7035
Publisher :
Academic Press, San Diego, United States - California