Searching peripheral blood mononuclear cells of children with viral respiratory tract infections preceding islet autoimmunity for viruses by high-throughput sequencing
To the Editor: Viral infections are discussed to cause autoimmune beta cell destruction leading to type 1 diabetes [1, 2]. Several recent prospective studies show evidence that respiratory tract infections are associated with an increased risk of beta cell autoimmunity and type 1 diabetes if they are encountered early in life (e.g., ). Consistent with this, the expression of an antiviral type 1 interferon (IFN) transcriptional signature is increased in peripheral blood mononuclear cells (PBMCs) of genetically predisposed infants before the development of beta cell autoantibodies . The upregulation of IFN-inducible genes is transient and correlates with recent self-reported incidence of respiratory infections.
Here, we hypothesized that we may be able to identify a pathogenic virus from PBMCs of infants who experienced respiratory tract infections before they developed beta cell autoantibodies. We considered that the identification of a virus in the blood of predisposed children...
KeywordsType 1 diabetes Respiratory tract infection PBMC Rotavirus Viral infection High-throughput sequencing VirCapSeq-VERT
Peripheral blood mononuclear cells
Glutamic acid decarboxylase 65-kDa Isoform
Insulinoma-associated protein 2
Zinc transporter 8
We wish to thank Sandra Hummel for coordinating the BABYDIET study, Annette Knopf for sample collection, Manja Jolink for data management, Boyhun Lee for bioinformatics support and Gregory J. Keough for project management. A part of this work has been performed as PhD thesis work (MH) at the Technical University of Munich.
This study was supported by Juvenile Diabetes Research Fund (JDRF-No 17-2012-16, JDRF-No 9-2011-253, FDRF-No 2-SRA-2015-13-Q-R), by Wellcome Trust (WT061858/091157), by grants from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD e.V.) and by iMed—the Helmholtz Initiative on Personalized Medicine. MH was supported by the Helmholtz Graduate School Environmental Health HELENA Lab Exchange Grant.
MH, AO, and RCF acquired the data. MH, KJ, EB, AGZ, and TB analyzed the data. MH, EB, AGZ, and TB wrote the manuscript. MH, CW, EB, AGZ, and TB designed the study. All authors revised and approved the final version of the manuscript. AGZ is responsible for the integrity of the work as a whole.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
The BABYDIET study was approved by the local Institutional Review Board (No. 329/00) and performed in accordance with ethical standards.
Written informed consent was obtained prior to study inclusion.