Relation of circulating concentrations of chemokine receptor CCR5 ligands to C-peptide, proinsulin and HbA1c and disease progression in type 1 diabetes.
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.
Pfleger
C
C
Institute for Clinical Diabetes Research at German Diabetes Centre, Leibniz Institute at Heinrich-Heine-University Duesseldorf, Auf'm Hennekamp 65, 40225 Duesseldorf, Germany. ch.pfleger@web.de
Kaas
A
A
Hansen
L
L
Alizadeh
B
B
Hougaard
P
P
Holl
R
R
Kolb
H
H
Roep
B O
BO
Mortensen
H B
HB
Schloot
N C
NC
D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002096:C-Peptide / Q000097:blood*; D054405:Chemokine CCL3 / Q000097:blood; D054407:Chemokine CCL4 / Q000097:blood; D018946:Chemokine CCL5 / Q000097:blood; D018925:Chemokines / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D007223:Infant; D008297:Male; D011384:Proinsulin / Q000097:blood*; D019713:Receptors, CCR5 / Q000097:blood*
D015415:Biomarkers; D002096:C-Peptide; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D006442:Glycated Hemoglobin; D011384:Proinsulin; D019713:Receptors, CCR5; C517652:hemoglobin A1c protein, human