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Diabetologia. 2004 Jul;47(7):1285-1291. doi: 10.1007/s00125-004-1441-4. Epub 2004 Jul 9.

T lymphocyte response against pancreatic beta cell antigens in fulminant Type 1 diabetes.

Author information

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.

PMID:
15243701
DOI:
10.1007/s00125-004-1441-4
[Indexed for MEDLINE]

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