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No Association Between Ljungan Virus Seropositivity and the Beta-cell Damaging Process in the Finnish Type 1 Diabetes Prediction and Prevention Study Cohort

Jääskeläinen, Anne J., PhD*; Nurminen, Noora, MSc; Kolehmainen, Pekka, PhD*,‡; Smura, Teemu, PhD*; Tauriainen, Sisko, PhD; Toppari, Jorma, MD, PhD§,¶; Ilonen, Jorma, MD, PhD; Veijola, Riitta, MD, PhD**; Knip, Mikael, MD, PhD††,‡‡,§§,¶¶; Hyöty, Heikki, MD, PhD†,‖‖; Vapalahti, Olli, MD, PhD*,**; Kallio-Kokko, Hannimari, PhD*

The Pediatric Infectious Disease Journal: March 2019 - Volume 38 - Issue 3 - p 314–316
doi: 10.1097/INF.0000000000002201
Pathogenesis and Host Response
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Background: Ljungan virus (LV) has not confirmed to associate with any human disease, but a possible connection with type 1 diabetes has been suggested. LV is a rodent-borne picornavirus that induces a diabetes-like condition in rodents. Approximately 30% of adults and 60% of children are seropositive in Finland. The Finnish Type 1 Diabetes Prediction and Prevention study enabled the use of very well characterized sample panels from children seroconverted to positivity for multiple islet autoantibodies during their prospective observation from birth; in addition, samples from age, sex, human leukocyte antigen (HLA), and residence area matched control children.

Methods: We analyzed LV IgG seroprevalence in 102 case children (65 had also developed type 1 diabetes), in addition to nondiabetic control children. LV and human parechovirus (HPeV) immunofluorescence assays were used to analyze LV and HPeV-specific IgG from 102 plasma samples taken at the time of islet autoantibody appearance and from 204 samples from the matched control children.

Results: Altogether 46.1% of the case and 50.7% of the control children were positive for LV IgG (odds ratio 0.8; 95% confidence interval, 0.47–1.36; P = 0.416) and 67.6% versus 79.8% were positive for HPeV IgG, respectively (odds ratio 0.49, 0.27–0.9, P = 0.023).

Conclusions: Thus, no risk associations between LV or HPeV-specific IgG and islet autoimmunity were observed. However, a trend for significantly higher prevalence of HPeV antibodies in control children (P = 0.023) suggests a possible protective association of this virus with islet autoimmunity.

From the *Department of Virology, Helsinki University and Helsinki University Hospital (HUSLAB), Finland

Department of Virology, School of Medicine, University of Tampere, Tampere, Finland

Department of Virology, University of Turku, Turku, Finland

§Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland

Department of Pediatrics, Turku University Hospital, Turku, Finland

Immunogenetics Laboratory, University of Turku and Turku University Hospital, Turku, Finland

**Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland

††Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

‡‡Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland

§§Folkhälsan Research Center, Helsinki, Finland

¶¶Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland

‖‖Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland

***Faculty of Veterinary Medicine, Department of Veterinary Biosciences, University of Helsinki, Finland.

Accepted for publication August 22, 2018.

The study was financially supported by the HUSLAB (Helsinki University Hospital, Helsinki, Finland), Sigrid Juselius Foundation, the Academy of Finland, Reino Lahtikari Foundation, and the Foundation for Diabetes Research in Finland. DIPP study has additionally been supported by grants from Juvenile Diabetes Research Foundation (JDRF) and the Competitive Research Funding of the Oulu, Tampere, and Turku University Hospitals.

The authors have no conflicts of interest to disclose.

Address for correspondence: Anne J. Jääskeläinen, PhD, Department of Virology, Helsinki University and Helsinki University Hospital, POB 21 (Haartmaninkatu 3), FIN-00014 University of Helsinki, Finland. E-mail: anne.jaaskelainen@helsinki.fi.

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