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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.
Exp Clin Endocrinol Diabetes. 2010 Jan; 118(1):38-46.EC

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.

Authors+Show Affiliations

Department of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19834879

Citation

Chatzigeorgiou, A E., et al. "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." Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association, vol. 118, no. 1, 2010, pp. 38-46.
Chatzigeorgiou AE, Lembessis PE, Mylona-Karagianni CF, et al. 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. Exp Clin Endocrinol Diabetes. 2010;118(1):38-46.
Chatzigeorgiou, A. E., Lembessis, P. E., Mylona-Karagianni, C. F., Tsouvalas, E. A., Diamanti-Kandarakis, E., & Kamper, E. F. (2010). 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. Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association, 118(1), 38-46. https://doi.org/10.1055/s-0029-1224151
Chatzigeorgiou AE, et al. 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. Exp Clin Endocrinol Diabetes. 2010;118(1):38-46. PubMed PMID: 19834879.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Chatzigeorgiou,A E, AU - Lembessis,P E, AU - Mylona-Karagianni,C F, AU - Tsouvalas,E A, AU - Diamanti-Kandarakis,E, AU - Kamper,E F, Y1 - 2009/10/15/ PY - 2009/10/17/entrez PY - 2009/10/17/pubmed PY - 2010/5/4/medline SP - 38 EP - 46 JF - Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association JO - Exp Clin Endocrinol Diabetes VL - 118 IS - 1 N2 - 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. SN - 1439-3646 UR - https://www.unboundmedicine.com/medline/citation/19834879/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_ L2 - http://www.thieme-connect.com/DOI/DOI?10.1055/s-0029-1224151 DB - PRIME DP - Unbound Medicine ER -