R Kotani1, M Nagata2, A Imagawa3,4, H Moriyama1, H Yasuda1, J Miyagawa4, T Hanafusa3, K Yokono1. 1. Division of Internal and Geriatric Medicine, Department of Development and Aging, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. 2. Division of Internal and Geriatric Medicine, Department of Development and Aging, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. nagata@med.kobe-u.ac.jp. 3. First Department of Internal Medicine, Osaka Medical College, Japan. 4. Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan.
Abstract
AIMS/HYPOTHESIS: Fulminant Type 1 diabetes is a novel subtype of Type 1 diabetes that involves the abrupt onset of insulin-deficient hyperglycaemia. This subtype appears to be non-autoimmune because of the absence of diabetes-related autoantibodies in the serum, and of insulitis in pancreatic biopsy specimens. The pathogenesis of the disease is still unknown. In this study, we investigated whether T cell autoimmune responses are involved in fulminant Type 1 diabetes. METHODS: Cellular immune responses to beta cell autoantigens were studied by enzyme-linked immunospot (ELISPOT) assay in 13 fulminant Type 1 diabetic patients and 49 autoantibody-positive autoimmune Type 1 diabetic patients. Results were compared with those of 18 Type 2 diabetic patients, six secondary diabetic patients (diabetes due to chronic pancreatitis) and 35 healthy controls. RESULTS: Nine of 13 (69.2%) GAD-reactive Th1 cells, and three of 12 (25%) insulin-B9-23-reactive Th1 cells were identified in fulminant Type 1 diabetic patients by ELISPOT, as in autoantibody-positive Type 1 diabetic patients. Four fulminant Type 1 diabetic patients possessed the highly diabetes-resistant allele DR2, three of whom had GAD-reactive Th1 cells in the periphery. CONCLUSIONS/ INTERPRETATION: Peripheral immune reaction was observed in 69.2% of fulminant Type 1 diabetic patients, indicating that autoreactive T cells might contribute, at least in part, to the development of fulminant Type 1 diabetes.
AIMS/HYPOTHESIS: Fulminant Type 1 diabetes is a novel subtype of Type 1 diabetes that involves the abrupt onset of insulin-deficient hyperglycaemia. This subtype appears to be non-autoimmune because of the absence of diabetes-related autoantibodies in the serum, and of insulitis in pancreatic biopsy specimens. The pathogenesis of the disease is still unknown. In this study, we investigated whether T cell autoimmune responses are involved in fulminant Type 1 diabetes. METHODS: Cellular immune responses to beta cell autoantigens were studied by enzyme-linked immunospot (ELISPOT) assay in 13 fulminant Type 1 diabeticpatients and 49 autoantibody-positive autoimmune Type 1 diabeticpatients. Results were compared with those of 18 Type 2 diabeticpatients, six secondary diabeticpatients (diabetes due to chronic pancreatitis) and 35 healthy controls. RESULTS: Nine of 13 (69.2%) GAD-reactive Th1 cells, and three of 12 (25%) insulin-B9-23-reactive Th1 cells were identified in fulminant Type 1 diabeticpatients by ELISPOT, as in autoantibody-positive Type 1 diabeticpatients. Four fulminant Type 1 diabeticpatients possessed the highly diabetes-resistant allele DR2, three of whom had GAD-reactive Th1 cells in the periphery. CONCLUSIONS/ INTERPRETATION: Peripheral immune reaction was observed in 69.2% of fulminant Type 1 diabeticpatients, indicating that autoreactive T cells might contribute, at least in part, to the development of fulminant Type 1 diabetes.