T-cell function in anti-GAD65 +diabetes with residual β-cell function

Abstract

We have recently reported that in patients with anti-glutamic acid decarboxylase (GAD) 65 +diabetes with residual β-cell function, most with a ‘high-titer’ (>10 U/ml) required insulin within 5 years, whereas most with a ‘low-titer’ (1.3–9.9 U/ml) did not need insulin for over 15–20 years after the onset. We therefore examined T-cell function to evaluate the difference between the high-titer and low-titer groups. Interleukin (IL)-10 production upon polyclonal activation was significantly lower in the high-titer group than in the low-titer group. The serum level of interferon-inducible protein-10 (IP-10) was higher in the high-titer than the low-titer group. Although GAD65-reactive CD4 +cells in the periphery were detected in both groups, a significant positive correlation between serum IP-10 level and the number of GAD65-reactive CD4 +cells was observed only in the high-titer group. Therefore, it has been speculated that the co-existence of GAD65-reactive IFN-γ-producing CD4 +cells and a high serum IP-10 level may be important for rapid disease progression as seen in the high-titer group. Based upon these results, T-cell function is considered to be different between the high-titer and low-titer groups in anti-GAD65 +diabetes with residual β-cell function, supporting our previous findings regarding the clinical outcome of insulin-dependence in the two groups.