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


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-gamma-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 (0.3 +/- 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-gamma-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.
Shimada
Akira
A
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. asmd@sc.keio.ac.jp
Kodama
Keiichi
K
Morimoto
Jiro
J
Oikawa
Yoichi
Y
Irie
Junichiro
J
Nakagawa
Yoshinori
Y
Matsubara
Koichi
K
Maruyama
Taro
T
Saruta
Takao
T
D000368:Aged; D001323:Autoantibodies / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007527:Isoenzymes / Q000276:immunology*; D008297:Male; D008875:Middle Aged
D001323:Autoantibodies; D007527:Isoenzymes; D007371:Interferon-gamma; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2