title: A Histological Study of Fulminant Type 1 Diabetes Mellitus Related to Human Cytomegalovirus Reactivation.
abstract: Fulminant type 1 diabetes mellitus (T1DM) is thought to be partly caused by virus infection.
  
  
  
  This study investigated the mechanism of β cell destruction in fulminant T1DM after drug-induced hypersensitivity syndrome (DIHS).
  
  
  
  We determined the localization of human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6), and Epstein-Barr virus (EBV) and the expression of interferon regulatory factor 3 (IRF3) and viral receptors of Z-DNA binding protein 1 (ZBP1) and retinoic acid-inducible gene I (RIG-I), together with inflammatory cells, by immunohistochemistry of the autopsy pancreas of a patient with fulminant T1DM with DIHS and in seven subjects with normal glucose tolerance who underwent pancreatectomy.
  
  
  
  HCMV-positive cells were detected in islets and exocrine areas in the patient with fulminant T1DM. Greater numbers of macrophages and CD4+ and CD8+ T lymphocytes had infiltrated into HCMV-positive islets than into HCMV-negative islets, and 52.6% of HCMV-positive cells were also positive for IRF3. α Cells expressed IRF3, ZBP1, or RIG-I. No HCMV-positive cells were detected in the control subjects. HHV-6-positive, but not EBV-positive, cells were present in the patient and the control subjects.
  
  
  
  These findings indicate that the immunoresponse caused by HCMV infection was associated with β cell injury.
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita "565-0871", Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Yoneda
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita "565-0871", Japan.|Department of Internal Medicine (I), Osaka Medical College, Takatsuki "569-8686", Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Imagawa
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita "565-0871", Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Fukui
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita "565-0871", Japan.
authors.forename: Sae
authors.initials: S
authors.lastname: Uno
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita "565-0871", Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Kozawa
authors.affiliation: Internal Medicine, Konan Hospital, Kobe "658-0064", Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sakai
authors.affiliation: Internal Medicine, Konan Hospital, Kobe "658-0064", Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yumioka
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita "565-0871", Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwahashi
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita "565-0871", Japan.
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D000368:Aged; D001707:Biopsy, Needle; D016022:Case-Control Studies; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000472:pathogenicity*; D003586:Cytomegalovirus Infections / Q000503:physiopathology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000821:virology; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism*; D008297:Male; D016601:RNA-Binding Proteins; D012016:Reference Values; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D014775:Virus Activation
chemical_list: D004268:DNA-Binding Proteins; D050838:Interferon Regulatory Factor-3; D016601:RNA-Binding Proteins; C485731:ZBP1 protein, human