Serum Th1 (CXCL10) and Th2 (CCL2) chemokine levels in children with newly diagnosed Type 1 diabetes: a longitudinal study.
OBJECTIVE
Cell-mediated immunity and pro-inflammatory cytokines are implicated in the pathogenesis of Type 1 diabetes. The aim of this study was to investigate whether circulating chemokines involved in T-helper 1 (CXCL10) and T-helper 2 (CCL2) autoimmunity are increased in children with Type 1 diabetes at onset and follow-up.


METHODS
Serum CXCL10 and CCL2 were measured in 96 children with newly diagnosed Type 1 diabetes, 59 age-matched first-degree relatives of diabetic children and 40 age-matched non-diabetic children with no family history of diabetes. In the diabetic children, an additional serum sample was obtained a median of 16 months after diagnosis.


RESULTS
Serum CXCL10 levels were significantly higher in Type 1 children than in relatives or control children (P < 0.001); 44.7% of patients had a serum CXCL10 level >or= 2 standard deviation above the mean value of the control group vs. 3.4% of relatives (P < 0.0001). In contrast, serum CCL2 levels were similar in patients, relatives and control subjects. In the Type 1 diabetic patients at follow-up, CXCL10 was significantly reduced vs. baseline (P = 0.01), while CCL2 did not change.


CONCLUSIONS
In children with newly diagnosed Type 1 diabetes, raised serum CXCL10 and normal CCL2 concentrations signal a predominant T-helper 1-driven autoimmune process, which shifts toward T-helper 2 immunity over the first 1-2 years from diagnosis.
Antonelli
A
A
Department of Internal Medicine and Metabolism Unit, CNR Institute of CLinical Physiology, University of Pisa, Pisa, Italy. a.antonelli@med.unipi.it
Fallahi
P
P
Ferrari
S M
SM
Pupilli
C
C
d'Annunzio
G
G
Lorini
R
R
Vanelli
M
M
Ferrannini
E
E
D018932:Chemokine CCL2 / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D002648:Child; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology*; D008137:Longitudinal Studies; D008297:Male; D012372:ROC Curve; D019707:Receptors, Chemokine / Q000097:blood / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D013997:Time Factors
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D019707:Receptors, Chemokine; D016753:Interleukin-10