Low gene expression levels of activating receptors of natural killer cells (NKG2E and CD94) in patients with fulminant type 1 diabetes.
Fulminant type 1 diabetes is an independent subtype of type 1 diabetes characterized by extremely rapid onset and absence of islet-related autoantibodies. However, detailed pathophysiology of this subtype is poorly understood. In this study, a comprehensive approach was applied to understand the pathogenesis of fulminant type 1 diabetes. We determined the genes that were differentially expressed in fulminant type 1 diabetes compared with type 1A diabetes and healthy control, using gene expression microarray in peripheral blood cells. Using volcano plot analysis, we found reduced expression of killer cell lectin-like receptor subfamily C, member 3 (KLRC3) which encodes NKG2E, a natural killer (NK) cell activating receptor, in fulminant type 1 diabetes, compared with healthy controls. This difference was confirmed by real-time RT-PCR among NK-enriched cells. The expression of KLRD1 (CD94), which forms heterodimer with NKG2E (KLRC3), was also reduced in NK-enriched cells in fulminant type 1 diabetes. Furthermore, flow cytometry showed significantly lower proportion of NK cells among peripheral blood mononuclear cells (PBMCs) in fulminant type 1 diabetes than in healthy controls. In patients with fulminant type 1 diabetes, the relative proportion of NK cells correlated significantly with the time period between onset of fever to the appearance of hyperglycemic-related symptoms. We conclude the presence of reduced NK activating receptor gene expression and low proportion of NK cells in fulminant type 1 diabetes.
['Nakata|Shinsuke|S|', 'Imagawa|Akihisa|A|', 'Miyata|Yugo|Y|', 'Yoshikawa|Atsushi|A|', 'Kozawa|Junji|J|', 'Okita|Kohei|K|', 'Funahashi|Tohru|T|', 'Nakamura|Seiji|S|', 'Matsubara|Kenichi|K|', 'Iwahashi|Hiromi|H|', 'Shimomura|Iichiro|I|']
D000328:Adult D003922:Diabetes Mellitus, Type 1 D005260:Female D005434:Flow Cytometry D006801:Humans D007694:Killer Cells, Natural D007963:Leukocytes, Mononuclear D008297:Male D055654:NK Cell Lectin-Like Receptor Subfamily C D051920:NK Cell Lectin-Like Receptor Subfamily D D020411:Oligonucleotide Array Sequence Analysis D020133:Reverse Transcriptase Polymerase Chain Reaction D059467:Transcriptome
natural killer Fulminant type 1 diabetes Microarray killer cell lectin-like receptor subfamily C, member 3 KLRC3 NK NK cell peripheral blood mononuclear cells PBMCs CTLA-4 EMC FITC GAD GAPDH HLA ICA IL18RAP MHC PE cytotoxic T-lymphocyte antigen 4 encephalomyocarditis fluorescein isothiocyanate glutamic acid decarboxylase glyceraldehyde 3-phosphate dehydrogenase human leukocyte antigen interleukin 18 receptor accessory protein islet-cell antibodies major histocompatibility complex phycoerythrin