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

Akira Shimada, Keiichi Kodama, Jiro Morimoto, Yoichi Oikawa, Junichiro Irie, Yoshinori Nakagawa, Koichi Matsubara, Taro Maruyama, Takao Saruta

Research output: Contribution to journalArticle

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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 (03 ± 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.

Original languageEnglish
Pages (from-to)378-386
Number of pages9
JournalAnnals of the New York Academy of Sciences
Volume1005
DOIs
Publication statusPublished - 2003

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Medical problems
Type 1 Diabetes Mellitus
Autoantibodies
T-cells
Antigens
Cytokines
T-Lymphocytes
Flow cytometry
Flow Cytometry
Blood
Research Design
Cells
Diabetes
Staining and Labeling
Serum

Keywords

  • Autoimmunity
  • GAD
  • IFN-γ
  • T cell
  • Type 1 diabetes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Shimada, A., Kodama, K., Morimoto, J., Oikawa, Y., Irie, J., Nakagawa, Y., ... Saruta, T. (2003). Detection of GAD-reactive CD4+ cells in so-called "type 1B" diabetes. Annals of the New York Academy of Sciences, 1005, 378-386. https://doi.org/10.1196/annals.1288.063

Detection of GAD-reactive CD4+ cells in so-called "type 1B" diabetes. / Shimada, Akira; Kodama, Keiichi; Morimoto, Jiro; Oikawa, Yoichi; Irie, Junichiro; Nakagawa, Yoshinori; Matsubara, Koichi; Maruyama, Taro; Saruta, Takao.

In: Annals of the New York Academy of Sciences, Vol. 1005, 2003, p. 378-386.

Research output: Contribution to journalArticle

Shimada, A, Kodama, K, Morimoto, J, Oikawa, Y, Irie, J, Nakagawa, Y, Matsubara, K, Maruyama, T & Saruta, T 2003, 'Detection of GAD-reactive CD4+ cells in so-called "type 1B" diabetes', Annals of the New York Academy of Sciences, vol. 1005, pp. 378-386. https://doi.org/10.1196/annals.1288.063
Shimada, Akira ; Kodama, Keiichi ; Morimoto, Jiro ; Oikawa, Yoichi ; Irie, Junichiro ; Nakagawa, Yoshinori ; Matsubara, Koichi ; Maruyama, Taro ; Saruta, Takao. / Detection of GAD-reactive CD4+ cells in so-called "type 1B" diabetes. In: Annals of the New York Academy of Sciences. 2003 ; Vol. 1005. pp. 378-386.
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AU - Shimada, Akira

AU - Kodama, Keiichi

AU - Morimoto, Jiro

AU - Oikawa, Yoichi

AU - Irie, Junichiro

AU - Nakagawa, Yoshinori

AU - Matsubara, Koichi

AU - Maruyama, Taro

AU - Saruta, Takao

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N2 - 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 (03 ± 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.

AB - 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 (03 ± 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.

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KW - GAD

KW - IFN-γ

KW - T cell

KW - Type 1 diabetes

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