Serum Th1 (CXCL10) and Th2 (CCL2) chemokine levels in children with newly diagnosed Type 1 diabetes: a longitudinal study.

ABSTRACT

AIMS: 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.