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    Clin Immunol. 2008 Jul;128(1):57-65. Epub 2008 Apr 22.

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

    Pfleger C, Kaas A, Hansen L, Alizadeh B, Hougaard P, Holl R, Kolb H, Roep BO, Mortensen HB, Schloot NC; Hvidøre Study Group On Childhood Diabetes.

    Collaborators (20)
    Aanstoot HJ, de Beaufort C, Chiarelli F, Dahl-Jørgensen K, Göthner HB, Danne T, Garandeau P, Greene SA, Hoey H, Holl RW, Kocova M, Martul P, Matsuura N, Mortensen HB, Robertson KJ, Schoenle EJ, Swift P, Tsou RM, Vanelli M, Aman JA.

    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

    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.

    PMID: 18434252 [PubMed - indexed for MEDLINE]

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