title: T lymphocyte response against pancreatic beta cell antigens in fulminant Type 1 diabetes.
abstract: 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.
authors.affiliation: 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.
authors.forename: R
authors.initials: R
authors.lastname: Kotani
authors.affiliation: 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.
authors.forename: M
authors.initials: M
authors.lastname: Nagata
authors.affiliation: First Department of Internal Medicine, Osaka Medical College, Japan.|Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Imagawa
authors.affiliation: 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.
authors.forename: H
authors.initials: H
authors.lastname: Moriyama
authors.affiliation: 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.
authors.forename: H
authors.initials: H
authors.lastname: Yasuda
authors.affiliation: Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Miyagawa
authors.affiliation: First Department of Internal Medicine, Osaka Medical College, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hanafusa
authors.affiliation: 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.
authors.forename: K
authors.initials: K
authors.lastname: Yokono
mesh_terms: 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*
chemical_list: D001323:Autoantibodies; D006442:Glycated Hemoglobin