title: Low gene expression levels of activating receptors of natural killer cells (NKG2E and CD94) in patients with fulminant type 1 diabetes.
abstract: 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.
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Nakata
authors.forename: Akihisa
authors.initials: A
authors.lastname: Imagawa
authors.forename: Yugo
authors.initials: Y
authors.lastname: Miyata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yoshikawa
authors.forename: Junji
authors.initials: J
authors.lastname: Kozawa
authors.forename: Kohei
authors.initials: K
authors.lastname: Okita
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Seiji
authors.initials: S
authors.lastname: Nakamura
authors.forename: Kenichi
authors.initials: K
authors.lastname: Matsubara
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwahashi
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000235:genetics / Q000276:immunology*
chemical_list: C527062:KLRC3 protein, human; C497869:KLRD1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D
keywords: CTLA-4; EMC; FITC; Fulminant type 1 diabetes; GAD; GAPDH; HLA; ICA; IL18RAP; KLRC3; MHC; Microarray; NK; NK cell; PBMCs; 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; killer cell lectin-like receptor subfamily C, member 3; major histocompatibility complex; natural killer; peripheral blood mononuclear cells; phycoerythrin