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

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2008-07, Vol.128 (1), p.57-65
• Main Authors: Pfleger, C, Kaas, A, Hansen, L, Alizadeh, B, Hougaard, P, Holl, R, Kolb, H, Roep, B.O, Mortensen, H.B, Schloot, N.C
• Format: Article
• Language: English
• Subjects: Adolescent; Allergy and Immunology; Biological and medical sciences; Biomarkers - blood; C-peptide; C-Peptide - blood; CCL3/MIP-1alpha; CCL4/MIP-1beta; CCL5/RANTES; Chemokine CCL3 - blood; Chemokine CCL4 - blood; Chemokine CCL5 - blood; Chemokines - blood; Child; Child, Preschool; Children; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; Disease Progression; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzyme-Linked Immunosorbent Assay; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glycated Hemoglobin A - analysis; Humans; Infant; Inflammation; Male; Medical sciences; Proinsulin; Proinsulin - blood; Receptors, CCR5 - blood; Remission; Type 1 diabetes mellitus
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2008.03.458

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.