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Exp Clin Endocrinol Diabetes 2010; 118(1): 38-46
DOI: 10.1055/s-0029-1224151
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

CD40 Expression and its Association with Low-grade Inflammation in a Greek Population of Type 1 Diabetic Juveniles: Evidence for Differences in CD40 mRNA Isoforms Expressed by Peripheral Blood Mononuclear Cells

A. E. Chatzigeorgiou1 , P. E. Lembessis1 , C. F. Mylona-Karagianni2 , E. A. Tsouvalas2 , E. Diamanti-Kandarakis3 , E. F. Kamper1
  • 1Department of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
  • 2Second Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Panagiotis and Aglaia Kyriakou Pediatric Hospital, Athens, Greece
  • 3Endocrine Section, First Department of Medicine, Medical School, Laiko General Hospital, University of Athens, Athens, Greece
Further Information

Publication History

received 22.04.2009 first decision 08.05.2009

accepted 11.05.2009

Publication Date:
15 October 2009 (online)

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Abstract

Background: CD40 signalling has been associated with the pathogenesis of autoimmune diseases and diseases with low-grade chronic inflammation.

Objective: To investigate, early in the course of type 1 diabetes (T1DM) patients, the expression of CD40 system components, as well as to explore the association of plasma and urine concentrations of CD40 with known inflammatory markers in T1DM.

Methods: Plasma, urine and peripheral blood mononuclear cells (PBMCs) from 70 T1DM patients without clinically detected chronic complications and 40 healthy controls (HCs) were examined using ELISA, western-blot, semi-quantitative RT-PCR and DNA-sequencing.

Results: Patients had significantly higher plasma soluble CD40 (sCD40) levels associated with higher Interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9) and CRP levels compared with healthy controls. This difference was also evident between poorly and well-controlled diabetic patients. The elevated plasma sCD40 levels do not appear to be due to diminished renal excretion since sCD40 concentrations in the urine were also elevated, suggesting an increased CD40 production. An upregulation of PBMCs’ CD40 was evident in T1DM patients associated with higher sCD40, IL-6 and CRP levels. Furthermore, the main CD40 isoform (isoform-I) was solely expressed in poorly controlled diabetics’ PBMCs, who also demonstrated cellular CD40 upregulation, higher plasma CD40, CRP, IL-6 and MMP-9 levels compared with the well-controlled diabetics and the control group, who co-expressed type I and II isoforms.

Conclusions: Homeostatic dysregulation of CD40 and its association with inflammatory markers in T1DM patients, especially in those with poor glycaemic control, implies a pathophysiological role of CD40 in the low-grade inflammatory process in T1DM.

Key words

type 1 diabetes (T1DM) - CD40 - inflammation - PBMC - isoforms - IL-6

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Correspondence

Asst. Prof. E. F. Kamper

Department of Experimental Physiology

Medical School, National and Kapodistrian

University of Athens

75 M.Asias Str., GR-115 27, Athens, Greece

Phone: 0030-210-7462595

Fax: 0030-210-7462594

Email: ekamper@med.uoa.gr

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