Koichi Matsubara

Detection of GAD-reactive CD4+ cells in so-called "type 1B" diabetes

Abstract: Objective—Although the majority of type 1 diabetes is considered to be type 1A, some patients with type 1 diabetes have no islet‐associated autoantibody in their serum. This type of type 1 diabetes has usually been diagnosed as type 1B on the basis of islet‐associated autoantibody‐negativity. In this study, we tried to demonstrate the existence of islet‐associated antigen‐specific T cells in type 1 diabetes without islet‐associated autoantibody. Research Design and Methods—Peripheral blood samples were obtained from 110 Japanese diabetic patients, including 15 type 2 diabetic patients. Measurement of islet‐associated antigen‐specific cytokine response was performed by intracellular cytokine staining for flow cytometry. Results—The number of GAD‐reactive IFN‐γ‐producing CD4+ cells in 50,000 CD4+ cells in diabetics with type 1B (113.6 ± 34.6, median 45), type 1A (132.4 ± 33.3, median 25), and LADA (154.4 ± 44.1, median 20) was higher than that in type 2 diabetics (0.3 ± 0.3, median 0) and control subjects (3.8 ± 2.4, median 0). When the normal upper limit of the number of GAD‐reactive CD4+ cells was set at the mean + 3SD of values in control subjects, at least half (52.4%) of the so‐called “type 1B” patients were positive for GAD‐reactive IFN‐γ‐producing CD4+ cells, a significantly larger proportion than that in type 2 diabetics (0%; p < 0.001). Conclusions—Assessment of T cell reactivity against islet‐associated antigen may contribute to the diagnosis of “autoimmune‐related” type 1 diabetes.