T lymphocyte response against pancreatic beta cell antigens in fulminant Type 1 diabetes.
OBJECTIVE
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
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.
Kotani
R
R
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
M
M
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.
Imagawa
A
A
First Department of Internal Medicine, Osaka Medical College, Japan.|Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan.
Moriyama
H
H
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.
Yasuda
H
H
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.
Miyagawa
J
J
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan.
Hanafusa
T
T
First Department of Internal Medicine, Osaka Medical College, Japan.
Yokono
K
K
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.
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006650:Histocompatibility Testing; D006801:Humans; D007111:Immunity, Cellular; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D006442:Glycated Hemoglobin