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Elevated Serum IP-10 Levels Observed in Type 1 Diabetes

¹ Division of Endocrinology, Keio University School of Medicine
² Tokyo University School of Medicine, Tokyo, Japan

OBJECTIVE—Although most patients with type 1 diabetes are considered to have T-cell–mediated autoimmune disease, a method of measuring of pancreatic ß-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) cells 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 patients, and the levels of autoantibodies (GAD and insulinoma-associated protein-2 [IA-2]) and IP-10 were measured. Diabetic patients positive for either 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 antigen–specific responses, peripheral blood from patients stimulated with or without GAD was used, and intracellular cytokine staining for flowcytometry was performed.

RESULTS—The Ab⁺ and Ab^- type 1 groups both showed a significantly higher serum IP-10 level than the healthy subjects (P < 0.001 and P < 0.05, respectively), and the IP-10 level in the recent-onset Ab⁺ subgroup was significantly higher than that in the established (longstanding) Ab⁺ subgroup (P < 0.002). Furthermore, there was a significant positive correlation between the serum IP-10 level and the number of GAD-reactive -interferon–producing CD4⁺ cells in the Ab⁺ type 1 group (P < 0.007).

CONCLUSIONS—Our findings demonstrate that measurement of serum IP-10 concentrations is useful in patients with type 1 diabetes.

Abbreviations: Ab⁺, autoantibody positive • Ab^-, autoantibody negative • ADA, American Diabetes Association • BSA, bovine serum albumin • ELISA, enzyme-linked immunosorbent assay • IFN-, -interferon • IP-10, interferon-inducible protein-10 • LADA, latent autoimmune diabetes in adults • PBS, phosphate-buffered saline • RT, room temperature

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