Elevated serum IP-10 levels observed in type 1 diabetes

OBJECTIVE - Although most patients with type 1 diabetes are considered to h ave T-cell-mediated autoimmune disease, a method of measuring of pancreatic beta -cell-specific T-cell function in cases of type 1 diabetes has yet to be established. Here, we focused on interferon-inducible protein-10 (IP-10 ), a chemokine that promotes the migration of activated T-helper 1 (Th1) ce lls and measured serum IP-10 levels in patients with human type 1 diabetes, which is regarded as a Th1-mediated disease. RESEARCH DESIGN AND METHODS - Serum samples were obtained from diabetic pat ients, and the levels of autoantibodies (GAD and insulinoma-associated prot ein-2 [IA-2]) and IP-10 were measured. Diabetic patients positive for eithe r or both of the autoantibodies were classified as Ab(+) type 1, and those negative for both were classified as Ab(-) type 1. To evaluate islet antige n-specific responses, peripheral blood from patients stimulated with or wit hout GAD was used, and intracellular cytokine staining for flowcytometry wa s performed. RESULTS - The Ab(+) and Ab(-) type 1 groups both showed a significantly hig her serum IP-10 level than the healthy subjects (P < 0.001 and P < 0.05, re spectively), and the IP-10 level in the recent-onset Ab(+) subgroup was sig nificantly higher than that in the established (longstanding) Abi subgroup (P < 0.002). Furthermore, there was a significant positive correlation betw een the serum IP-10 level and the number of GAD-reactive <gamma>-interferon -producing CD4+ cells in the Abi type 1 group (P < 0.007). CONCLUSIONS - Our findings demonstrate that measurement of serum IP-10 conc entrations is useful in patients with type 1 diabetes.