Diabetologia

pp 1–8

Detection of enteroviruses in stools precedes islet autoimmunity by several months: possible evidence for slowly operating mechanisms in virus-induced autoimmunity

  • Hanna Honkanen
  • Sami Oikarinen
  • Noora Nurminen
  • Olli H. Laitinen
  • Heini Huhtala
  • Jussi Lehtonen
  • Tanja Ruokoranta
  • Minna M. Hankaniemi
  • Valérie Lecouturier
  • Jeffrey W. Almond
  • Sisko Tauriainen
  • Olli Simell
  • Jorma Ilonen
  • Riitta Veijola
  • Hanna Viskari
  • Mikael Knip
  • Heikki Hyöty
Article

DOI: 10.1007/s00125-016-4177-z

Cite this article as:
Honkanen, H., Oikarinen, S., Nurminen, N. et al. Diabetologia (2017). doi:10.1007/s00125-016-4177-z

Abstract

Aims/hypothesis

This case–control study was nested in a prospective birth cohort to evaluate whether the presence of enteroviruses in stools was associated with the appearance of islet autoimmunity in the Type 1 Diabetes Prediction and Prevention study in Finland.

Methods

Altogether, 1673 longitudinal stool samples from 129 case children who turned positive for multiple islet autoantibodies and 3108 stool samples from 282 matched control children were screened for the presence of enterovirus RNA using RT-PCR. Viral genotype was detected by sequencing.

Results

Case children had more enterovirus infections than control children (0.8 vs 0.6 infections per child). Time-dependent analysis indicated that this excess of infections occurred more than 1 year before the first detection of islet autoantibodies (6.3 vs 2.1 infections per 10 follow-up years). No such difference was seen in infections occurring less than 1 year before islet autoantibody seroconversion or after seroconversion. The most frequent enterovirus types included coxsackievirus A4 (28% of genotyped viruses), coxsackievirus A2 (14%) and coxsackievirus A16 (11%).

Conclusions/interpretation

The results suggest that enterovirus infections diagnosed by detecting viral RNA in stools are associated with the development of islet autoimmunity with a time lag of several months.

Keywords

EnterovirusGenotypingRT-PCRStool samplesType 1 diabetes

Abbreviations

DIPP

Type 1 Diabetes Prediction and Prevention

IAA

Insulin antibody

ICA

Islet cell antibody

IA-2A

Insulinoma-associated protein 2 antibodies

VP1

Viral protein 1

Supplementary material

125_2016_4177_MOESM1_ESM.pdf (115 kb)
ESM Figures(PDF 114 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Hanna Honkanen
    • 1
  • Sami Oikarinen
    • 1
    • 2
  • Noora Nurminen
    • 1
  • Olli H. Laitinen
    • 3
    • 4
  • Heini Huhtala
    • 5
  • Jussi Lehtonen
    • 1
  • Tanja Ruokoranta
    • 3
  • Minna M. Hankaniemi
    • 3
    • 4
  • Valérie Lecouturier
    • 6
  • Jeffrey W. Almond
    • 6
  • Sisko Tauriainen
    • 7
  • Olli Simell
    • 8
    • 9
  • Jorma Ilonen
    • 10
  • Riitta Veijola
    • 11
  • Hanna Viskari
    • 1
    • 12
  • Mikael Knip
    • 13
    • 14
    • 15
    • 16
  • Heikki Hyöty
    • 1
    • 2
  1. 1.Department of VirologyUniversity of TampereTampereen yliopistoFinland
  2. 2.Fimlab LaboratoriesPirkanmaa Hospital DistrictTampereFinland
  3. 3.Vactech LtdTampereFinland
  4. 4.BioMediTechUniversity of TampereTampereFinland
  5. 5.School of Health SciencesUniversity of TampereTampereFinland
  6. 6.Sanofi-PasteurMarcy L’EtoileFrance
  7. 7.Department of VirologyUniversity of TurkuTurkuFinland
  8. 8.Department of Pediatrics and Research Centre of Applied and Preventive Cardiovascular MedicineUniversity of TurkuTurkuFinland
  9. 9.Department of Pediatrics and Adolescent MedicineTurku University HospitalTurkuFinland
  10. 10.Immunogenetics LaboratoryUniversity of Turku and Turku University HospitalTurkuFinland
  11. 11.Department of Pediatrics, PEDEGO Research Unit, Medical Research CenterOulu University Hospital and University of OuluOuluFinland
  12. 12.Department of Internal MedicineTampere University HospitalTampereFinland
  13. 13.Children’s Hospital, University of Helsinki and Helsinki University Central HospitalHelsinkiFinland
  14. 14.Research Programs Unit, Diabetes and ObesityUniversity of HelsinkiHelsinkiFinland
  15. 15.Department of PediatricsTampere University HospitalTampereFinland
  16. 16.Folkhälsan Research CenterHelsinkiFinland