Context: Fulminant type 1 diabetes mellitus (T1DM) is thought to be partly caused by virus infection. Objective: This study investigated the mechanism of β cell destruction in fulminant T1DM after drug-induced hypersensitivity syndrome (DIHS). Methods: 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. Results: 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. Conclusions: These findings indicate that the immunoresponse caused by HCMV infection was associated with β cell injury.
Context: Fulminant type 1 diabetes mellitus (T1DM) is thought to be partly caused by virus infection. Objective: This study investigated the mechanism of β cell destruction in fulminant T1DM after drug-induced hypersensitivity syndrome (DIHS). Methods: 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. Results: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. Conclusions: These findings indicate that the immunoresponse caused by HCMV infection was associated with β cell injury.
Authors: Somayeh Sabouri; Mehdi A Benkahla; William B Kiosses; Teresa Rodriguez-Calvo; Jose Zapardiel-Gonzalo; Ericka Castillo; Matthias G von Herrath Journal: J Autoimmun Date: 2019-12-06 Impact factor: 7.094
Authors: Seul Gi Yoo; Kyung Do Han; Kyoung Hwa Lee; Yeonju La; Da Eun Kwon; Sang Hoon Han Journal: Diabetes Metab J Date: 2019-01-21 Impact factor: 5.376