J Ilonen

University of Turku, Turku, Province of Western Finland, Finland

Are you J Ilonen?

Claim your profile

Publications (323)1339.4 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Importance: The role of microbial exposure during early life in the development of type 1 diabetes mellitus is unclear. Objective: To investigate whether animal contact and other microbial exposures during infancy are associated with the development of preclinical and clinical type 1 diabetes. Design, Setting, and Participants: A birth cohort of children with HLA antigen-DQB1-conferred susceptibility to type 1 diabetes was examined. Participants included 3143 consecutively born children at 2 hospitals in Finland between 1996 and 2004. Exposures: The following exposures during the first year of life were assessed: indoor and outdoor dogs and cats, farm animals, farming, visit to a stable, day care, and exposure to antibiotics during the first week of life. Main Outcomes and Measures: Clinical and preclinical type 1 diabetes were used as outcomes. The latter was defined as repeated positivity for islet-cell antibodies plus for at least 1 of 3 other diabetes-associated autoantibodies analyzed and/or clinical type 1 diabetes. The autoantibodies were analyzed at 3- to 12-month intervals since the birth of the child. Results: Children exposed to an indoor dog, compared with otherwise similar children without an indoor dog exposure, had a reduced odds of developing preclinical type 1 diabetes (adjusted odds ratio [OR], 0.47; 95% CI, 0.28-0.80; P = .005) and clinical type 1 diabetes (adjusted OR, 0.40; 95% CI, 0.14-1.14; P = .08). All of the other microbial exposures studied were not associated with preclinical or clinical diabetes: the odds ratios ranged from 0.74 to 1.58. Conclusions and Relevance: Among the 9 early microbial exposures studied, only the indoor dog exposure during the first year of life was inversely associated with the development of preclinical type 1 diabetes. This finding needs to be confirmed in other populations.
    JAMA Pediatrics 06/2014; · 4.28 Impact Factor
  • The Journal of allergy and clinical immunology 05/2014; · 12.05 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Vitamin D has immunomodulatory properties, such as regulation of FOXP3 expression and regulatory T-cell activity. Our aim was to investigate whether plasma 25-hydroxyvitamin D [25(OH)D] concentrations associate with the development of β-cell autoimmunity and the transcriptional activity of FOXP3 or vitamin D3 convertase gene (CYP27B1) in CD4+ memory T cells. We studied 83 Finnish and 32 Estonian children participating in the DIABIMMUNE and DIPP studies. Twenty-nine Finnish and six Estonian children tested positive for at least one diabetes-associated autoantibody. The plasma concentrations of 25(OH)D and 1,25(OH)2 D were analyzed with an enzyme immunoassay. Gene expression of FOXP3 and CYP27B1 in the isolated CD4+ memory T cells was studied with RT-qPCR. Vitamin D status did not differ between subjects positive and negative for β-cell autoantibodies. Finnish children had higher vitamin D status than Estonian children (p < 0.001). FOXP3 expression was higher in Estonian CD4+ memory T cell samples than in Finnish samples (p < 0.01) also when including in both groups only children with serum 25(OH)D concentrations in the range of 50 to 80 nmol/l (p < 0.001). These findings do not support a crucial role of circulating 25(OH)D as a regulator of β-cell autoimmunity or FOXP3 expression. This article is protected by copyright. All rights reserved.
    Diabetes/Metabolism Research and Reviews 04/2014; · 2.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: AIMS/HYPOTHESIS: An association between increased length/height and weight gain and risk of type 1 diabetes (T1D) has been reported in children. We set out to investigate the potential contribution of T1D human leukocyte antigen (HLA) risk genotypes to this association in two countries with a contrasting disease incidence. METHODS: In Estonia and Finland, length and weight were monitored up to the age of 24 months in 688 subjects. According to their HLA genotypes, the children were divided into four groups, those with very high, high or moderate risk for T1D, as well as a neutral/control group. Relative length and weight (SDS) were assessed and compared at 3, 6, 12, 18 and 24 months using World Health Organization (WHO) growth curves. RESULTS: The mean relative length at the age of 24 months was lower in the group with the very high risk HLA genotype compared to the controls (p < 0.05). The mean relative weight differed between those two groups at the age of 12, 18 and 24 months (p < 0.05). When Estonian and Finnish cohorts were analyzed separately, the relative length showed similar but non-significant trends in both countries, while in Estonia the changes in weight at some time points still remained significant (p < 0.05). CONCLUSIONS: Children with the highest HLA-conferred risk for T1D gained less weight and length during the first 24 months of life, and this feature was more pronounced in the Estonian children.
    Diabetes/Metabolism Research and Reviews 01/2014; 30(1):60-8. · 2.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To further characterise the effect of the HLA-B∗39 allele on type 1 diabetes risk we assessed its role in different HLA-DR/DQ haplotypes and genotypes using 1764 nuclear families with a diabetic child collected in the framework of the Finnish Paediatric Diabetes Register. HLA assays were based on sequence specific hybridization using lanthanide labelled oligonucleotide probes. Transmissions of major HLA-DR/DQ haplotypes with and without the HLA-B∗39 allele to diabetic index cases were analysed by direct haplotype and allele counting. The HLA-B∗39 allele significantly increased the disease risk conferred by DRB1∗04:04-DQA1∗03-DQB1∗03:02 and (DR8)-DQB1∗04 haplotypes. The same effect was observed on genotype level as disease association for the HLA-B∗39 allele was observed in multiple genotypes containing DRB1∗04:04-DQA1∗03-DQB1∗03:02 or (DR8)-DQB1∗04 haplotypes. Finally we considered the two common subtypes of the HLA-B∗39 allele, B∗39:01 and B∗39:06 and observed their unequal distribution when stratified for specific DR-DQ haplotypes. The risk for type 1 diabetes conferred by certain DR/DQ haplotypes is modified by the presence of the HLA-B∗39 and this confirms the independent disease predisposing effect of the HLA-B∗39 allele. The results can be applied in enhancing the sensitivity and specificity of DR/DQ based screening programs for subjects at disease risk.
    Human Immunology. 01/2014; 75(1):65–70.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background We set out to define the characteristics of humoral autoimmunity against ZnT8 in children and adolescents with newly diagnosed T1D in relation to age and metabolic status at diagnosis, human leucocyte antigen (HLA) genotype and family history of T1D. MethodsA total of 2115 subjects <15 years of age were analysed for antibodies against zinc transporter 8, ICA, GADA, IAA, IA-2A, HLA DR-DQ genotype, blood pH, plasma glucose and β-hydroxybutyrate concentrations. Their family history of T1D was also recorded. ResultsZinc transporter 8 antibodies (ZnT8A) were detected in 63% of the cases. ZnT8A positivity was associated with older age at diagnosis (mean 8.2 years versus 7.5 years, p < 0.001). Seven subjects (0.3%) had ZnT8A as their single autoantibody. Diabetic ketoacidosis at diagnosis was less common among subjects with ZnT8A than among those without (16% versus 20%, p = 0.012). The prevalence of ZnT8A was decreased in DR3/DR4 heterozygotes when compared with those with other DR combinations (p < 0.001). Subjects with the neutral DR13-DQB1*0604 haplotype tested more frequently positive for ZnT8A than the rest of the population (p < 0.001). A positive family history of T1D showed no association with ZnT8A prevalence or levels. Conclusions Antibodies for ZnT8 is related to age and metabolic status at diagnosis as well as HLA genotype but does not significantly improve the detection rate of β-cell autoimmunity in Finnish children and adolescents affected by T1D. Copyright © 2013 John Wiley & Sons, Ltd.
    Diabetes/Metabolism Research and Reviews 11/2013; 29(8). · 2.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To further characterise the effect of the HLA-B∗39 allele on type 1 diabetes risk we assessed its role in different HLA-DR/DQ haplotypes and genotypes using 1764 nuclear families with a diabetic child collected in the framework of the Finnish Paediatric Diabetes Register. HLA assays were based on sequence specific hybridization using lanthanide labelled oligonucleotide probes. Transmissions of major HLA-DR/DQ haplotypes with and without the HLA-B∗39 allele to diabetic index cases were analysed by direct haplotype and allele counting. The HLA-B∗39 allele significantly increased the disease risk conferred by DRB1∗04:04-DQA1∗03-DQB1∗03:02 and (DR8)-DQB1∗04 haplotypes. The same effect was observed on genotype level as disease association for the HLA-B∗39 allele was observed in multiple genotypes containing DRB1∗04:04-DQA1∗03-DQB1∗03:02 or (DR8)-DQB1∗04 haplotypes. Finally we considered the two common subtypes of the HLA-B∗39 allele, B∗39:01 and B∗39:06 and observed their unequal distribution when stratified for specific DR-DQ haplotypes. The risk for type 1 diabetes conferred by certain DR/DQ haplotypes is modified by the presence of the HLA-B∗39 and this confirms the independent disease predisposing effect of the HLA-B∗39 allele. The results can be applied in enhancing the sensitivity and specificity of DR/DQ based screening programs for subjects at disease risk.
    Human immunology 09/2013; · 2.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Human parechoviruses (HPeVs) are RNA viruses associated mainly with mild gastrointestinal and respiratory infections in children and also cause neonatal sepsis and CNS infections. Human enteroviruses, close relatives of HPeVs, associate with the development of type 1 diabetes. In this study, the potential role of HPeV infections in promoting beta cell autoimmunity was investigated by analyzing stool samples of 54 prediabetic case and 134 healthy control children for the presence of HPeV RNA and comparing the derived infection frequencies. All 188 children were participants of the Finnish prospective Diabetes Prediction and Prevention study. Viral RNA was screened for using an HPeV-specific RT-PCR method coupled to liquid hybridization of the PCR product. The overall HPeV infection frequency did not differ between prediabetic case and control children. However, case boys had more HPeV positive samples in the 6-month period before becoming autoantibody positive, when compared to the matching time-period in controls (P < 0.01). HPeV infection at a young age does not appear to play a major role in the development of beta-cell autoimmunity. In boys, however, HPeVs showed time-dependent association with the first detection of diabetes-associated autoantibodies. Thus, in boys, HPeV infections cannot be excluded as a gender-specific risk factor which promotes the development of type 1 diabetes. J. Med. Virol. 85:1619-1623, 2013. © 2013 Wiley Periodicals, Inc.
    Journal of Medical Virology 09/2013; 85(9):1619-23. · 2.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Enterovirus infections in childhood have been associated with a reduced risk of atopy in cross-sectional studies. OBJECTIVE: To study the relation between enterovirus infections in the first 2 years of life and atopic disease with IgE sensitization in a prospective study setting. METHODS: This was a nested case-control study among children who had been followed from birth. Neutralizing antibodies against 12 enterovirus serotypes were analysed at the age of 2 years from 71 atopic children and 142 non-atopic control children. Atopy was defined as having an atopic disease and IgE antibodies against at least one aeroallergen by the age of 5 years. RESULTS: Cumulative exposure to different enterovirus serotypes was inversely associated with atopy [odds ratio (OR) 0.73; 95% confidence interval (CI): 0.56-0.96]. The most pronounced protection was seen when echoviruses were analysed as a separate group (OR 0.63; 95%CI: 0.46-0.88). CONCLUSIONS AND CLINICAL RELEVANCE: We propose that exposure to several different enteroviruses in early childhood is inversely associated with atopic diseases. Our results support the hypothesis that repeated microbial infections in early life may protect from atopic sensitization and atopic diseases.
    Clinical & Experimental Allergy 06/2013; 43(6):625-632. · 4.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To study the associations between timing and diversity of introduction of complementary foods during infancy and atopic sensitization in 5-year-old children. In the Finnish DIPP (Type 1 Diabetes Prediction and Prevention) birth cohort (n = 3781), data on the timing of infant feeding were collected up to the age of 2 years and serum IgE antibodies toward four food and four inhalant allergens measured at the age of 5 years. Logistic regression was used for the analyses. Median duration of exclusive and total breastfeeding was 1.4 (interquartile range: 0.2-3.5) and 7.0 (4.0-11.0) months, respectively. When all the foods were studied together and adjusted for confounders, short duration of breastfeeding decreased the risk of sensitization to birch allergen; introduction of oats <5.1 months and barley <5.5 months decreased the risk of sensitization to wheat and egg allergens, and oats additionally associated with milk, timothy grass, and birch allergens. Introduction of rye <7.0 months decreased the risk of sensitization to birch allergen. Introduction of fish <6 months and egg ≤11 months decreased the risk of sensitization to all the specific allergens studied. The introduction of <3 food items at 3 months was associated with sensitization to wheat, timothy grass, and birch allergens; the introduction of 1-2 food items at 4 months and ≤4 food items at 6 months was associated with all endpoints, but house dust mite. These results were particularly evident among high-risk children when the results were stratified by atopic history, indicating the potential for reverse causality. The introduction of complementary foods was consecutively done, and with respect to the timing of each food, early introduction of complementary foods may protect against atopic sensitization in childhood, particularly among high-risk children. Less food diversity as already at 3 months of age may increase the risk of atopic sensitization.
    Allergy 04/2013; 68(4):507-16. · 5.88 Impact Factor
  • Source
  • Source
  • A. P. Laine, M. Knip, J. Ilonen
    [Show abstract] [Hide abstract]
    ABSTRACT: Currently more than 50 type 1 diabetes (T1D) loci outside the human leukocyte antigen (HLA)-region have been established in large European and/or North American populations. Our aim was to attempt to replicate these findings in the less heterogenic Finnish population and to explore evidence for genetic heterogeneity. We analyzed 1761 Finnish T1D trio families for association in 31 T1D loci (25 confirmed and 6 have inconsistent prior evidence). Families were categorized into nine different subgroups according to potential features that reflect underlying genetic heterogeneity in patients (age at diagnosis, sex and HLA genotypes). Seventeen confirmed loci and one nonconfirmed locus (1p31.1) presented significant evidence for association in the full data set. Magnitude and direction of effect was consistent with prior evidence. The strongest effects were seen at the insulin gene, PTPN22 and IL2RA regions. Tentative evidence of odds ratio (OR) heterogeneity within subgroups was seen in eight loci. Our findings were well in line with those reported in the latest meta-analyses using large admixed Caucasian populations, which concurs with the notion that the currently confirmed T1D loci, that have been discovered and replicated mostly in diverse populations, are common to all European populations. The observed effect modifications by subgrouping require validation in later studies with more statistical power.
    Tissue Antigens 01/2013; 82(1):35-42. · 2.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: More than 50 loci outside the human leukocyte antigen (HLA) region have been confirmed to affect type 1 diabetes (T1D) risk but their effect on beta-cell autoimmunity is poorly defined. We analyzed the association of 35 single nucleotide polymorphism (SNP) markers previously associated with T1D with the presence of disease-predictive autoantibodies at the time of T1D diagnosis. SUBJECTS AND METHODS: The study cohort comprised 1554 children diagnosed with T1D before the age of 15 yr. The associations between various genotypes and positivity for antibodies against islet cells [islet cell antibodies (ICA)], insulin [insulin autoantibodies (IAA)], glutamic acid decarboxylase (GADA), islet antigen 2 (IA2A), and zinc transporter 8 (ZnT8A) were analyzed. RESULTS: INS gene polymorphism rs689 and IKZF4 polymorphism (rs1701704) were strongly associated with IAA positivity at the time of T1D diagnosis (p = 0.000004 and 0.00044, respectively). The presence of the T1D-risk conferring INS AA genotype was associated with IAA. In contrast, the presence of the susceptible C allele of the IKZF4 marker was inversely associated with IAA. The INS and IKZF4 polymorphisms were not significantly associated with ICA, GADA, IA2A, or ZnT8A positivity. CONCLUSIONS: Both INS and IKZF4 polymorphisms modified the probability of IAA positivity at time of T1D onset but the inverse association of IKZF4 risk allele with IAA suggests that the IKZF4 polymorphism is involved in a pathway of beta-cell autoimmunity alternate to the route characterized by IAA and development of T1D in early childhood. The IKZF4 gene encodes Eos, which is implicated to play an important role in Treg programming where this gene might exert its influence on T1D risk.
    Pediatric Diabetes 01/2013; · 2.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: AIMS/HYPOTHESIS: Patients with type 1 diabetes and kidney disease have a higher risk of cardiovascular events. HLA class II genes are expressed on infiltrated inflammatory cells and smooth-muscle cells in atherosclerotic plaques. We hypothesised that HLA class II haplotypes or genotypes might influence the risk of cardiovascular complications and death in Finnish type 1 diabetic patients. METHODS: We included 3,082 patients with type 1 diabetes from the Finnish Diabetic Nephropathy Study. We analysed the 12 and ten most common HLA II haplo- and genotypes, respectively, using χ (2) tests. The positive findings were analysed with three differently adjusted regression models with cardiovascular morbidity and death as endpoints. Different kidney status groups were analysed separately. RESULTS: At baseline, the common (DR1/10)-DQB1*05:01 haplotype (20.4%) and the (DR1/10)-DQB1*05:01/DRB1*04:01-DQB1*03:02 genotype (8.7%) were independently associated with cardiovascular disease in all kidney status groups, except in patients with normal AER. At follow-up (9.45 years; range 0.1-16.1 years), the (DR1/10)-DQB1*05:01/DRB1*04:01-DQB1*03:02 genotype was associated with cardiovascular mortality rates in patients with normal AER and microalbuminuria. CONCLUSIONS/INTERPRETATION: The (DR1/10)-DQB1*05:01 haplotype and the (DR1/10)-DQB1*05:01/DRB1*04:01-DQB1*03:02 genotype are independently associated with cardiovascular events and death in Finnish type 1 diabetic patients.
    Diabetologia 08/2012; 55(11):2963-2969. · 6.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To explore the association between maternal dietary fat and fatty acid (FA) intake during lactation, and the risk of asthma in the offspring by the age of 5 years. The subjects comprised 1798 mother-child pairs from the Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study. Dietary intake was assessed by a validated 181-item food frequency questionnaire, which covered the third month of lactation. The cumulative incidence of asthma was assessed at the age of 5 years with a questionnaire modified from the International Study of Asthma and Allergies in Childhood (ISAAC). Cox proportional hazards regression was used for statistical analysis. The maternal use of margarines during lactation was associated with a marginally increased risk of asthma [hazard ratio (HR) for user vs. nonuser 1.96, 95% confidence interval (CI) 1.01-3.82, p = 0.047] after adjusting for putative confounders. The maternal intakes of n-3 polyunsaturated FA (PUFA) and fish during lactation were not associated with the risk of asthma. Maternal use of margarines during lactation was weakly associated with an increased risk of asthma in the offspring at the age of 5 years. Other fats or FAs during lactation were not associated with the risk of asthma. However, the nonadherence to dietary recommendations regarding especially fats of our study population may restrict the generalizability of our results.
    Acta Paediatrica 05/2012; 101(8):e337-43. · 1.97 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: T cell recognition of gliadin from dietary gluten is essential for the pathogenesis of coeliac disease (CD). The aim of the present study was to analyse whether gliadin-specific T cells are detectable in the circulation of children with newly diagnosed coeliac disease by using a sensitive carboxfluorescein diacetate succinimidyl ester (CFSE) dilution method. Peripheral blood CD4(+) T cell responses were analysed in 20 children at diagnosis of CD and compared to those in 64 healthy control children carrying the CD-associated human leucocyte antigen (HLA)-DQ2 or -DQ8 alleles. Deamidated gliadin (gTG)-specific T cells were detectable in the peripheral blood of more than half the children with CD (11 of 20, 55%) compared to 15 of 64 (23.4%) of the control children (P = 0.008). Proliferative responses to gTG were also significantly stronger in children with CD than in controls (P = 0.01). In contrast, T cells specific to native gliadin were detectable at comparable frequencies in children with CD (two of 19, 10.5%) and controls (13 of 64, 20.3%). gTG-specific T cells had a memory phenotype more often than those specific to native gliadin in children with CD (P = 0.02), whereas controls had similar percentages of memory cells in both stimulations. Finally, gTG-specific CD4(+) T cells had a higher expression of the gut-homing molecule β7 integrin than those specific to the control antigen tetanus toxoid. Collectively, our current results demonstrate that the frequency of circulating memory CD4(+) T cells specific to gTG but not native gliadin is increased in children with newly diagnosed CD.
    Clinical & Experimental Immunology 05/2012; 168(2):207-14. · 3.41 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the study was to investigate the timing of the appearance of autoantibodies associated with type 1 diabetes between birth and puberty, the natural fate of these autoantibodies and the predictive power of autoantibody concentrations for early progression to clinical diabetes. Children were recruited to the Type 1 Diabetes Prediction and Prevention Project, an ongoing study based on HLA-conferred genetic risk. Autoantibodies against islet cells, insulin, GAD65 and islet antigen 2 were analysed at 3-12 month intervals, starting from birth. During the follow-up, 1,320 children (18.4% of the cohort of 7,165 children) were autoantibody positive in at least one sample. Altogether, 184 autoantibody-positive children progressed to type 1 diabetes. Seroconversion occurred at an early age in the progressors (median 1.5 years), among whom 118 (64%) and 150 (82%) seroconverted to autoantibody positivity before the age of 2 and 3 years, respectively. The incidence of seroconversion peaked at 1 year of age. Compared with other autoantibody-positive children, the median autoantibody levels were already markedly higher 3 to 6 months after the seroconversion in children who later progressed to diabetes. Early initiation of autoimmunity and rapid increases in autoantibody titres strongly predict progression to overt diabetes before puberty, emphasising the importance of early life events in the development of type 1 diabetes.
    Diabetologia 03/2012; 55(7):1926-36. · 6.49 Impact Factor
  • Source
    Nature Genetics 12/2011; 44(1):3-5. · 35.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Enteral virus infections and early introduction of cow's milk (CM)-based formula are among the suggested triggers of type 1 diabetes (T1D)-associated autoimmunity, although studies on their role have remained contradictory. Here, we aimed to analyse whether interactions between these factors might clarify the controversies. The study population comprised 107 subjects developing positivity for at least two T1D-associated autoantibodies and 446 control subjects from the Finnish diabetes prediction and prevention cohort. Enterovirus, rotavirus, adenovirus, respiratory syncytial virus and bovine insulin-binding antibodies were analysed from prospective serum samples at 3-24 months of age. Data on infant cow's milk exposure were available for 472 subjects: 251 subjects were exposed to cow's milk before 3 months of age and 221 subjects later in infancy. Signs of an enterovirus infection by 12 months of age were associated with the appearance of autoimmunity among children who were exposed to cow's milk before 3 months of age. Cox regression analysis revealed a combined effect of enterovirus infection and early cow's milk exposure for the development of ICA and any of the biochemically defined autoantibodies (p = 0.001), of IAA (p = 0.002), GADA (p = 0.001) and IA-2A (p = 0.013). The effect of enterovirus infection on the appearance of T1D-associated autoimmunity seems to be modified by exposure to cow's milk in early infancy suggesting an interaction between these factors. Moreover, these results provide an explanation for the controversial findings obtained when analysing the effect of any single one of these factors on the appearance of T1D-associated autoimmunity.
    Diabetes/Metabolism Research and Reviews 09/2011; 28(2):177-85. · 2.97 Impact Factor

Publication Stats

6k Citations
1,339.40 Total Impact Points

Institutions

  • 1983–2014
    • University of Turku
      • • Department of Virology
      • • Department of Paediatrics
      • • Department of Medical Biochemistry and Genetics
      • • Department of Neurology
      Turku, Province of Western Finland, Finland
  • 2010–2013
    • University of Eastern Finland
      Kuopio, Eastern Finland Province, Finland
    • Diabetes Clinic for Children and Adolescents
      Muenster, North Rhine-Westphalia, Germany
  • 1994–2013
    • University of Tampere
      • • School of Health Sciences
      • • Medical School
      • • Institute of Biomedical Sciences
      Tampere, Western Finland, Finland
  • 2010–2012
    • National Institute for Health and Welfare, Finland
      • • Nutrition Unit
      • • Department of Lifestyle and Participation
      Helsinki, Southern Finland Province, Finland
  • 1998–2012
    • Turku University Hospital
      • Department of Pediatrics
      Turku, Western Finland, Finland
    • Kuopio University Hospital
      • Department of Paediatrics
      Kuopio, Province of Eastern Finland, Finland
  • 2008–2011
    • Pirkanmaa Hospital District
      Tammerfors, Province of Western Finland, Finland
  • 1985–2011
    • University of Helsinki
      • • The Hospital for Children and Adolescents
      • • Department of Dental Public Health
      • • Division of Nutrition
      • • Department of Pediatrics
      Helsinki, Province of Southern Finland, Finland
  • 2008–2010
    • University of Kuopio
      • Department of Clinical Microbiology
      Kuopio, Eastern Finland Province, Finland
  • 1978–2009
    • University of Oulu
      • • Department of Paediatrics
      • • Department of Medical Microbiology
      • • Department of Neurology
      Uleoborg, Oulu, Finland
  • 2006–2008
    • Linköping University
      • • Department of Clinical and Experimental Medicine (IKE)
      • • Faculty of Health Sciences
      Linköping, OEstergoetland, Sweden
  • 1970–2008
    • Lappeenranta University of Technology
      • Laboratory of Laser Processing
      Villmanstrand, Southern Finland Province, Finland
  • 2007
    • Åbo Akademi University
      Turku, Province of Western Finland, Finland
  • 1997–2006
    • Turku centre for biotechnology, finland
      Turku, Province of Western Finland, Finland
  • 1984–2006
    • National Public Health Institute
      Helsinki, Southern Finland Province, Finland
  • 2003–2004
    • Chumakov Institute of Poliomyelitis and Viral Encephalitides
      Moskva, Moscow, Russia
  • 1993–1995
    • SickKids
      Toronto, Ontario, Canada
  • 1992–1995
    • University of Toronto
      • Hospital for Sick Children
      Toronto, Ontario, Canada
  • 1988–1989
    • University of Alberta
      Edmonton, Alberta, Canada
  • 1986
    • Oulu University Hospital
      Uleoborg, Oulu, Finland