Advertisement

Acta Diabetologica

, Volume 55, Issue 8, pp 881–884 | Cite as

Searching peripheral blood mononuclear cells of children with viral respiratory tract infections preceding islet autoimmunity for viruses by high-throughput sequencing

  • Markus Hippich
  • Alexandra Oleynik
  • Komal Jain
  • Christiane Winkler
  • Ricardo C. Ferreira
  • Ezio Bonifacio
  • Anette-Gabriele Ziegler
  • Thomas Briese
Letter to the Editor

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., [3]). 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 [4]. 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...

Keywords

Type 1 diabetes Respiratory tract infection PBMC Rotavirus Viral infection High-throughput sequencing VirCapSeq-VERT 

Abbreviations

IFN

Interferon

PBMCs

Peripheral blood mononuclear cells

GAD65

Glutamic acid decarboxylase 65-kDa Isoform

IA-2

Insulinoma-associated protein 2

ZnT8

Zinc transporter 8

Notes

Acknowledgements

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.

Funding

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.

Authors’ contribution

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.

Ethical standard

The BABYDIET study was approved by the local Institutional Review Board (No. 329/00) and performed in accordance with ethical standards.

Informed consent

Written informed consent was obtained prior to study inclusion.

Supplementary material

592_2018_1138_MOESM1_ESM.doc (138 kb)
Supplementary material 1 (DOC 138 kb)

References

  1. 1.
    Honeyman MC, Coulson BS, Stone NL et al (2000) Association between rotavirus infection and pancreatic ilset autoimmunity in children at risk of developing type 1 diabetes. Diabetes 49:1319–1324CrossRefPubMedGoogle Scholar
  2. 2.
    Lee HS, Briese T, Winkler C et al (2013) Next-generation sequencing for viruses in children with rapid-onset type 1 diabetes. Diabetologia 56(8):1705–1711.  https://doi.org/10.1007/s00125-013-2924-y CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Beyerlein A, Donnachie E, Jergens S, Ziegler A (2016) Infections in early life and development of type 1 diabetes. JAMA 315(17):1899–1901.  https://doi.org/10.1001/jama.2016.2181 CrossRefPubMedGoogle Scholar
  4. 4.
    Ferreira RC, Guo H, Coulson RMR et al (2014) A type I interferon transcriptional signature precedes autoimmunity in children genetically at risk for type 1 diabetes. Diabetes 63(63):2538–2550.  https://doi.org/10.2337/db13-1777/-/DC1 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Moon S, Wang Y, Dennehy P, Simonsen KA, Zhang J, Jiang B (2012) Antigenemia, RNAemia, and innate immunity in children with acute rotavirus diarrhea. FEMS Immunol Med Microbiol 64(3):382–391.  https://doi.org/10.1111/j.1574-695X.2011.00923.x CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental HealthMunich-NeuherbergGermany
  2. 2.Center for Infection and Immunity, Mailman School of Public HealthColumbia UniversityNew YorkUSA
  3. 3.Forschergruppe Diabetes e.V., at Helmholtz Zentrum München, German Research Center for EnvironmentalMunichGermany
  4. 4.JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research CentreUniversity of OxfordOxfordUK
  5. 5.DFG Center for Regenerative Therapies Dresden, Faculty of MedicineTechnische Universität DresdenDresdenGermany
  6. 6.Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD)Technische Universität DresdenDresdenGermany
  7. 7.Forschergruppe Diabetes, at Klinikum rechts der IsarTechnische Universität MünchenMunichGermany
  8. 8.Department of Epidemiology, Mailman School of Public HealthColumbia UniversityNew YorkUSA

Personalised recommendations