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

被引：49

作者：

Pfleger, C. ^{[1
]}

Kaas, A. ^{[2
]}

Hansen, L. ^{[3
]}

Alizadeh, B. ^{[4
]}

Hougaard, P. ^{[5
]}

Holl, R. ^{[6
]}

Kolb, H. ^{[1
]}

Roep, B. O. ^{[7
]}

Mortensen, H. B. ^{[2
]}

Schloot, N. C. ^{[1
,8
]}

机构：

[1] Univ Dusseldorf, Leibniz Inst, German Diabet Ctr, Inst Clin Diabet Res, D-40225 Dusseldorf, Germany

[2] Glostrup Univ Hosp, Dept Paediat, Glostrup, Denmark

[3] Novo Nordisk AS, Dev Projects, DK-2880 Bagsvaerd, Denmark

[4] Erasmus MC, Dept Epidemiol & Biostat, Rotterdam, Netherlands

[5] Univ So Denmark, Dept Stat, Odense, Denmark

[6] Univ Ulm, Dept Paediat, Ulm, Germany

[7] Leiden Univ, Med Ctr, Dept Immunohaematol & Blood & Transfus, Leiden, Netherlands

[8] Univ Dusseldorf, Ctr Internal Med, D-4000 Dusseldorf, Germany

来源：

CLINICAL IMMUNOLOGY | 2008年 / 128卷 / 01期

关键词：

CCL3/MIP-1; alpha; CCL4/MIP-1beta; CCL5/RANTES; proinsulin; C-peptide; inflammation; disease progression; children; type 1 diabetes mellitus; remission;

D O I：

10.1016/j.clim.2008.03.458

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：57 / 65

页数：9

共 36 条

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