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.

Additional Metadata
Keywords C-peptide, CCL3/MIP-1alpha, CCL4/MIP-1beta, CCL5/RANTES, Children, Disease progression, Inflammation, Proinsulin, Remission, Type 1 diabetes mellitus
Persistent URL dx.doi.org/10.1016/j.clim.2008.03.458, hdl.handle.net/1765/30458
Citation
Pfleger, C, Kaas, A, Hansen, L, Alizadeh, B.Z, Hougaard, P, Holl, R, … Schloot, N.C. (2008). Relation of circulating concentrations of chemokine receptor CCR5 ligands to C-peptide, proinsulin and HbA1c and disease progression in type 1 diabetes. Clinical Immunology, 128(1), 57–65. doi:10.1016/j.clim.2008.03.458