J Ilonen

University of Eastern Finland, Kuopio, Northern Savo, Finland

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Publications (486)2385.92 Total impact

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    ABSTRACT: The consumption of foods rich in n-3 polyunsaturated fatty acids has been proposed to protect against childhood asthma. This study explores the association of food consumption (including cow's milk (CM) free diet) in early life, and the risk of atopic and non-atopic asthma. Food intake of 182 children with asthma and 728 matched controls was measured using three-day food records, within the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) -Nutrition Study cohort. The diagnoses of food allergies came both from the written questionnaire and from the registers of the Social Insurance Institution. Conditional logistic regression with generalized estimating equations framework was used in the analyses. The diagnosis of cow's milk allergy (CMA) led to multiple dietary restrictions still evident at four years of age. Even after adjusting for CMA, higher consumption of CM products was inversely associated with the risk of atopic asthma and higher consumption of breast milk and oats inversely with the risk of non-atopic asthma. Early consumption of fish was associated with a decreased risk of all asthma. Dietary intake in early life combined with atopy history has a clear impact on the risk of developing asthma. Our results indicate that CM restriction due to CMA significantly increases and mediates the association between food consumption and childhood asthma risk. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Pediatric Allergy and Immunology 02/2015; · 3.38 Impact Factor
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    ABSTRACT: This study used next-generation sequencing (NGS) technologies to characterize the gut virome at the onset of islet autoimmunity. We conducted a case-control study nested within the Finnish Diabetes Prediction and Prevention cohort. The stool virome in 19 case children, who turned islet autoantibody positive before the age of 2 years and later developed clinical type 1 diabetes, and 19 tightly matched control subjects was analyzed using NGS performed from stool samples collected 3, 6, and 9 months before the onset of islet autoimmunity. Human virus findings were verified using real-time PCR. One or more human viruses were present in 10.4% and bacteriophages in 54% of the samples. The virome composition showed no association with islet autoimmunity. NGS was less sensitive and specific than real-time PCR. The present data suggest no dramatic changes in the gut virome shortly before the emergence of islet autoimmunity and emphasize the need of verification of mass sequencing results when viral exposure is assessed in association studies. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Diabetes care. 02/2015;
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    ABSTRACT: Islet autoantibodies, in addition to elevated blood glucose, define type 1 diabetes. These autoantibodies are detectable for a variable period of time before diabetes onset. Thus, the occurrence of islet autoantibodies is associated with the beginning of the disease process. The age at, and order in, which autoantibodies appear may be associated with different genetic backgrounds or environmental exposures, or both. Infants with HLA-DR high-risk genotypes (DR3/4, DR4/4, DR4/8 and DR3/3) were enrolled and prospectively followed with standardised autoantibody assessments quarterly throughout the first 4 years of life and then semi-annually thereafter. Autoantibodies appeared in 549/8,503 (6.5%) children during 34,091 person-years of follow-up. Autoantibodies at 3 (0.1%) and 6 (0.2%) months of age were rare. Of the 549, 43.7% had islet autoantibodies to insulin (IAA) only, 37.7% had glutamic acid decarboxylase autoantibodies (GADA) only, 13.8% had both GADA and IAA only, 1.6% had insulinoma antigen-2 only and 3.1% had other combinations. The incidence of IAA only peaked within the first year of life and declined over the following 5 years, but GADA only increased until the second year and remained relatively constant. GADA only were more common than IAA only in HLA-DR3/3 children but less common in HLA-DR4/8 children. Islet autoantibodies can occur very early in life and the order of appearance was related to HLA-DR-DQ genotype.
    Diabetologia 02/2015; · 6.88 Impact Factor
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    ABSTRACT: Colonization of the fetal and infant gut microbiome results in dynamic changes in diversity, which can impact disease susceptibility. To examine the relationship between human gut microbiome dynamics throughout infancy and type 1 diabetes (T1D), we examined a cohort of 33 infants genetically predisposed to T1D. Modeling trajectories of microbial abundances through infancy revealed a subset of microbial relationships shared across most subjects. Although strain composition of a given species was highly variable between individuals, it was stable within individuals throughout infancy. Metabolic composition and metabolic pathway abundance remained constant across time. A marked drop in alpha-diversity was observed in T1D progressors in the time window between seroconversion and T1D diagnosis, accompanied by spikes in inflammation-favoring organisms, gene functions, and serum and stool metabolites. This work identifies trends in the development of the human infant gut microbiome along with specific alterations that precede T1D onset and distinguish T1D progressors from nonprogressors. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cell Host & Microbe 02/2015; · 12.19 Impact Factor
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    ABSTRACT: AimsOur aim was to study whether immune responses to wheat-based proteins are related to the development of type 1 diabetes.Methods We analysed proliferative T-cell responses after in vitro gliadin, gluten, whole wheat, and tetanus toxoid stimulation with a carboxyfluorescein succinimidyl ester (CFSE) based T-cell proliferation assay in children at various phases of type 1 diabetes autoimmunity and in healthy autoantibody-negative control children.ResultsAt an early stage of beta cell autoimmunity the strength and frequencies of positive proliferation responses to gliadin, gluten, and whole wheat did not differ between newly seroconverted children positive for one islet autoantibody and the controls. However, in prediabetic children with at least two islet autoantibodies and also in children with newly diagnosed type 1 diabetes positive T-cell responses to gliadin were significantly less frequent and the strength of gliadin responses was reduced when compared to the controls. No differences were seen in T-cell responses to wheat-based antigens when comparing children with long-lasting type 1 diabetes with healthy controls.Conclusions/InterpretationDecreased in vitro T-cell responses to wheat-based antigens were observed in children with multiple islet autoantibodies and in those with newly diagnosed type 1 diabetes, probably reflecting a generally aberrant immune response during the development of type 1 diabetes.
    Pediatric Diabetes 01/2015; · 2.13 Impact Factor
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    ABSTRACT: We determined longitudinal serum proteomics profiles from children with HLA-conferred diabetes susceptibility to identify changes that could be detected before seroconversion and positivity for disease-associated autoantibodies. Comparisons were made between children who seroconverted and progressed to type 1 diabetes (progressors) and those who remained autoantibody negative, matched by age, gender, sample periodicity and risk group. The samples represented the pre-diabetic period and ranged from the age of 3 months to 12 years.Following immunoaffinity-depletion of the most abundant serum proteins, isobaric Tags for Relative and Absolute Quantification (iTRAQ) were used for sample labelling. Quantitative proteomic profiles were thus measured for 13 case-control pairs by HPLC-tandem mass spectrometry (LC-MS/MS). Additionally, a label free LC-MS/MS approach was used to analyze depleted sera from six case-control pairs.Importantly, differences in abundance of a set of proteins were consistently detected already before the appearance of autoantibodies in the progressors. On the basis of top scoring pair analysis, classification of such progressors was observed with a high success rate. Overall the data provides a reference of temporal changes in the serum proteome in healthy children and children who develop type 1 diabetes, including new protein candidates, the levels of which change prior to clinical diagnosis. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Diabetes 01/2015; · 7.90 Impact Factor
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    ABSTRACT: Dietary advanced glycation end products (AGEs) and their interactions with the receptor for AGEs (RAGE) may play a role in the pathogenesis of type 1 diabetes. This study set out to assess whether there is any association between circulating concentrations of soluble RAGE (sRAGE), AGEs, and their ratio with the appearance of diabetes-associated autoantibodies in children progressing to clinical diabetes. Serum concentrations of sRAGE, N-ε(carboxymethyl)lysine (CML) adducts and the sRAGE/CML ratio were analyzed in children who progressed to type 1 diabetes. The samples were taken at four time points: before seroconversion, at the time of the first autoantibody-positive sample, at the time of the first sample positive for multiple (>2) autoantibodies, and close to the disease diagnosis. Samples of autoantibody-negative controls matched for age, sex, and HLA-conferred diabetes risk were analyzed at corresponding time points. The prediabetic children had higher sRAGE concentrations before seroconversion (Pc = 0.03), at the appearance of multiple autoantibodies (Pc = 0.008), and close to diagnosis (Pc = 0.04). Close to diagnosis, the cases had lower CML concentrations than the controls (Pc = 0.004). Prediabetic children had a higher sRAGE/CML ratio than the controls before seroconversion (Pc = 0.008) and at diagnosis (Pc < 0.001). Prediabetic children have higher concentrations of sRAGE and a higher sRAGE/CML ratio than healthy controls. Circulating sRAGE concentrations seem to decline with the appearance of diabetes-predictive autoantibodies in children progressing to type 1 diabetes. The higher sRAGE/CML ratio in prediabetic children may reflect a higher AGE scavenger capacity. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Diabetes Care 01/2015; · 8.57 Impact Factor
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    ABSTRACT: We examined maternal dietary intake of fatty acids and foods which are sources of fatty acids during lactation and whether they are associated with the risk of preclinical and clinical type 1 diabetes in the offspring. The subjects comprised a cohort of 2,939 mother-child pairs from the prospective Type 1 Diabetes Prediction and Prevention Study. Composition of maternal diet during the third month of lactation was assessed by a validated food frequency questionnaire. Among the children with HLA-conferred susceptibility to type 1 diabetes, 172 developed preclinical and 81 clinical diabetes. Average follow-up for preclinical type 1 diabetes was 7.5 years (range 0.2-14.0 years) and for clinical type 1 diabetes 7.7 years (0.2-14.0 years). Maternal intake of fatty acids during lactation was not associated with the risk of type 1 diabetes in the offspring. After adjusting for putative confounders, maternal total consumption of red meat and meat products during lactation was associated both with increased risk for preclinical [hazard ratio (HR) 1.19, 95 % CI 1.02-1.40, p = 0.038] and clinical type 1 diabetes (HR 1.27, 95 % CI 1.06-1.52, p = 0.025). In particular, consumption of processed meat products showed an association with increased risk for type 1 diabetes (HR 1.23, 95 % CI 1.02-1.48, p = 0.045). Maternal use of vegetable oils was associated with increased risk for preclinical type 1 diabetes (HR 1.21, 95 % CI 1.03-1.41, p = 0.023). Maternal consumption of red meat, especially processed meat, during lactation may increase the risk of type 1 diabetes.
    Acta diabetologica. 01/2015;
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    ABSTRACT: Prediction of type 1 diabetes is based on the detection of multiple islet autoantibodies in subjects at increased genetic risk. Prediction of the timing of diagnosis is challenging, however. We assessed the utility of HbA1c in predicting the clinical disease in genetically predisposed children with multiple autoantibodies. Cord blood samples from 168,055 newborn infants were screened for class II HLA genotypes in Finland, and 14,876 children with increased genetic risk for type 1 diabetes were invited to regular follow-up including screening for diabetes-associated autoantibodies. When two or more autoantibodies were detected HbA1c was analyzed at each visit. During follow-up 466 children developed multiple (≥2) autoantibodies, and 201 (43%) of these were diagnosed with type 1 diabetes (progressors), while 265 remained disease-free (non-progressors) by December 2011. A 10% increase in HbA1c levels in samples taken 3-12 months apart predicted the diagnosis of clinical disease (HR 5.7, 95% CI 4.1-7.9), after a median time of 1.1 years (IQR 0.6-3.1) from the observed rise of HbA1c. If HbA1c was ≥5.9% (41 mmol/mol) in two consecutive samples, the median time to diagnosis was 0.9 years (IQR 0.3-1.5; HR 11.9, 95% CI 8.8-16.0). In conclusion, HbA1c is a useful biochemical marker when predicting time to diagnosis of type 1 diabetes in children with multiple autoantibodies. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Diabetes 12/2014; · 7.90 Impact Factor
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    ABSTRACT: Determinationof antibodies to synthetic deamidatedgliadin peptides (anti-DGP) may work as an alternative or complement the commonly used test for tissue transglutaminase antibodies (TGA) in the diagnosis of celiac disease (CD). We analyzed the performance of a time-resolved immunofluorometry (TR-IFMA) based anti-DGP assay in the diagnosis of CD in children and also retrospectively analyzed the appearance of anti-DGP antibodies before TGA seroconversion. The study included 92 children with biopsy-confirmed CD. Serum samples were taken at the time or just before the clinical diagnosis. The control group comprised of 82 TGA-negative children who were positive for HLA-DQ2 or -DQ8. Based on receiver operating characteristics (ROC) curves, the optimal cut-off value for IgA anti-DGP positivity was 153 arbitrary units (AU) with a sensitivity of 92.4% and specificity of 97.6% and that for IgG anti-DGP 119 AU, with a sensitivity of 97.8% and specificity of 97.6%. All of the 92 children with CD were either IgA or IgG anti-DGP positive at the time of diagnosis. Sera from 48 children with CD were also analyzed retrospectively before the diagnosis. Anti-DGP antibodies preceded TGA positivity in 35 of 48 CD children and appeared a median of one year earlier. The TR-IFMA assay for detecting anti-DGP antibodies shows high sensitivity and specificity for the diagnosis of CD in children. In a majority of our study population anti-DGP seropositivity preceded TGA positivity, indicating that earlier detection of CD may be possible by monitoring anti-DGP antibodies frequently in genetically susceptible children.
    Journal of pediatric gastroenterology and nutrition 12/2014; · 2.18 Impact Factor
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    ABSTRACT: Upregulation of IL-17 immunity and detrimental effects of IL-17 on human islets have been implicated in human type 1 diabetes. In animal models, the plasticity of Th1/Th17 cells contributes to the development of autoimmune diabetes. In this study, we demonstrate that the upregulation of the IL-17 pathway and Th1/Th17 plasticity in peripheral blood are markers of advanced β cell autoimmunity and impaired β cell function in human type 1 diabetes. Activated Th17 immunity was observed in the late stage of preclinical diabetes in children with β cell autoimmunity and impaired glucose tolerance, but not in children with early β cell autoimmunity. We found an increased ratio of IFN-γ/IL-17 expression in Th17 cells in children with advanced β cell autoimmunity, which correlated with HbA1c and plasma glucose concentrations in an oral glucose tolerance test, and thus impaired β cell function. Low expression of Helios was seen in Th17 cells, suggesting that Th1/Th17 cells are not converted thymus-derived regulatory T cells. Our results suggest that the development of Th1/Th17 plasticity may serve as a biomarker of disease progression from β cell autoantibody positivity to type 1 diabetes. These data in human type 1 diabetes emphasize the role of Th1/Th17 plasticity as a potential contributor to tissue destruction in autoimmune conditions. Copyright © 2014 by The American Association of Immunologists, Inc.
    Journal of immunology (Baltimore, Md. : 1950). 12/2014;
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    ABSTRACT: The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively follows 8,677 children enrolled from birth, who carry HLA-susceptibility genotypes for development of islet autoantibodies (IA) and type 1 diabetes (T1D). During the median follow-up time of 57 months, 350 children developed at least one persistent IA (GADA, IA-2A or mIAA) and 84 of them progressed to T1D. We genotyped 5,164 Caucasian children for 41 non-HLA SNPs that achieved genome-wide significance for association with T1D in the GWAS meta-analysis conducted by the Type 1 Diabetes Genetics Consortium. In TEDDY-participants carrying high-risk HLA-genotypes, eight SNPs achieved significant association to development of IA using time-to-event analysis (p<0.05), whereof four were significant after adjustment for multiple testing (p<0.0012): rs2476601 in PTPN22 (hazard ratio [HR] 1.54 [95% CI 1.27-1.88]), rs2292239 in ERBB3 (HR 1.33 [95% CI 1.14-1.55]), rs3184504 in SH2B3 (HR 1.38 [95% CI 1.19-1.61]) and rs1004446 in INS (HR 0.77 [0.66-0.90]). These SNPs were also significantly associated with T1D in particular: rs2476601 (HR 2.42 [95% CI 1.70-3.44]). Although genes in the HLA-region remain the most important genetic risk factors for T1D, other non-HLA genetic factors contribute to IA, a first step in the pathogenesis of T1D, and the progression of the disease. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Diabetes 11/2014; · 7.90 Impact Factor
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    ABSTRACT: Type I interferon induced MxA response can differentiate viral from bacterial infections, but MxA responses in rhinovirus or asymptomatic virus infections are not known.Objective To study MxA protein levels in healthy state and during respiratory virus infection of young children in an observational prospective cohort.Study designBlood samples and nasal swabs were collected from 153 and 77 children with and without symptoms of respiratory infections, respectively. Blood MxA protein levels were measured by an enzyme immunoassay and PCR methods were used for the detection of respiratory viruses in nasal swabs.ResultsRespiratory viruses were detected in 81% of symptomatic children. They had higher blood MxA protein levels (median [interquartile range]) than asymptomatic virus-negative children (695 [345–1370] μg/L vs. 110 [55–170] μg/L; p < 0.001). Within asymptomatic children, no significant difference was observed in MxA responses between virus-positive and virus-negative groups. A cut-off level of 175 μg/L had 92% sensitivity and 77% specificity for a symptomatic respiratory virus infection. Rhinovirus, respiratory syncytial virus, parainfluenza virus, influenza virus, coronavirus, and human metapneumovirus infections were associated with elevated MxA responses. Asymptomatic virus-negative children vaccinated with a live virus vaccine had elevated MxA protein levels (240 [120–540] μg/L), but significantly lower than children with an acute respiratory infection, who had not received vaccinations (740 [350–1425] μg/L; p < 0.001).Conclusion Blood MxA protein levels are increased in young children with symptomatic respiratory virus infections, including rhinovirus infections. MxA is an informative general marker for the most common acute virus infections.
    Journal of Clinical Virology 11/2014; · 3.47 Impact Factor
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    ABSTRACT: Coxsackievirus B4 (CV-B4) belongs to the genus Enterovirus within family Picornaviridae. To investigate target proteins recognised by T-cells in human enterovirus B infections, viral-encoded structural (VP0 [VP4 and VP2], VP1, VP3) and non-structural (2A, 2B, 2C, 3C and 3D) proteins were expressed and purified in E. coli. Peripheral blood of 19 healthy adult donors was used to create enterovirus-specific T-cell lines by repeated stimulation with CV-B4 cell lysate antigen. T-cell lines responded in individual patterns, and responses to all purified proteins were observed. The most often recognised enteroviral protein was VP0, which is the fusion between the most conserved structural proteins, VP4 and VP2. T-cell responses to VP0 were detected in 15 of 19 (79%) donor lines. Non-structural 2C protein was recognised in 11 of 19 (58%) lines, and 11 of 19 (58%) lines also had a response to 3D protein. Furthermore, responses to other non-structural proteins (2A, 2B and 3C) were also detected. T-cell responses did not correlate clearly to the individual HLA-DR-DQ phenotype or the history of past coxsackie B virus infections of the donors.
    Journal of General Virology 11/2014; · 3.53 Impact Factor
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    ABSTRACT: Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N=28,459). We identified 7 independent top SNPs (P<1x10(-6)) for birth length, of which 3 were novel and 4 were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The 3 novel SNPs were followed-up in 9 replication studies (Stage 2; N=11,995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1+2; ß=0.046, S.E.=0.008, P=2.46x10(-8), explained variance=0.05%). Rs905938 was also associated with infant length (N=28,228; P=5.54x10(-4)) and adult height (N=127,513; P=1.45x10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
    Human Molecular Genetics 10/2014; · 6.68 Impact Factor
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    ABSTRACT: The prevalence of immune-mediated diseases, such as allergies and type 1 diabetes, is on the rise in the developed world. In order to explore differences in the gene expression patterns induced in utero in infants born in contrasting standards of living and hygiene, we collected umbilical cord blood RNA samples from infants born in Finland (modern society), Estonia (rapidly developing society) and the Republic of Karelia, Russia (poor economic conditions). The whole blood transcriptome of Finnish and Estonian neonates differed from their Karelian counterparts, suggesting exposure to toll-like receptor (TLR) ligands and a more matured immune response in infants born in Karelia. These results further support the concept of a conspicuous plasticity in the developing immune system: the environmental factors that play a role in the susceptibility/protection towards immune-mediated diseases begin to shape the neonatal immunity already in utero and direct the maturation in accordance with the surrounding microbial milieu.
    Clinical Immunology 09/2014; · 3.99 Impact Factor
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    ABSTRACT: Background The study aimed to define the frequencies of type 1 diabetes-associated gene polymorphisms and their associations with various diabetes-associated autoantibodies in Egyptian children.Methods One hundred one children with type 1 diabetes and 160 healthy controls from the same region were studied for HLA-DQB1, -DQA1 and -DRB1 (DR4 subtypes) alleles, INS and PTPN22 gene polymorphisms (rs689 and rs2476601) and for diabetes-associated autoantibodies.ResultsMost diabetic children (77.2%) were positive for the HLA-(DR3)-DQA1*05-DQB1*02 (DR3-DQ2) haplotype compared to 26.2% of the controls (OR = 9.5; p < 0.001). HLA-DRB1*04:02-DQA1*03-DQB1*03:02 (DR4-DQ8) (26.7%, OR = 3.3; p < 0.001), DRB1*04:05-DQA1*03-DQB1*02 (DR4-DQ2) (23.8%, OR 5.2; p < 0.001) and DRB1*04:05-DQA1*03-DQB1*03:02 (DR4-DQ8) (8.9%, OR = 7.7; p = 0.007) were also significantly increased. HLA-(DR15)-DQB1*06:01, (DR13)-DQB1*06:03 and DRB1*04:03-DQA1*03-DQB1*03:02 were the most protective haplotypes with OR values from 0.04 to 0.06. Patients positive for DR3-DQ2 but negative for DR4 haplotypes had a high frequency of GAD antibodies (78%; p <0.001 vs. other genotypes) but only 26.6% of those with DR3-DQ2/DR4-DQ2 tested positive for GAD antibodies (p = 0.006 vs. other genotypes). Subjects with the DR4-DQ8 haplotype without DR3-DQ2 or DR4-DQ2 were more often positive for IA-2 and ZnT8 antibodies (55.5%; p =0.007 and 55.5%, p =0.01, respectively). The AA genotype of INS gene was more common in patients than controls (75.2% vs 59.5%, OR = 2.07; p = 0.018).Conclusions Besides a strong HLA-DR3-DQ2 association a relatively high frequency of the DR4-DQ2 haplotype characterized the diabetic population. The low frequency of autoantibodies in children with HLA-DR4-DQ2 may indicate specific pathogenetic pathways associated with this haplotype. This article is protected by copyright. All rights reserved.
    Diabetes/Metabolism Research and Reviews 09/2014; · 3.59 Impact Factor
  • Jorma Ilonen, Mikael Knip, Outi Vaarala
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    ABSTRACT: Autoantibodies against pancreatic islets are strong predictors of Type 1 diabetes. When persistent β-cell autoantibodies against at least two autoantigens are detected, the probability of diabetes is extremely high, although the time period before disease development can vary from days up to more than 20 years. Insulin autoantibodies or antibodies specific to glutamate decarboxylase 65 enzyme are in most cases, the first autoantibodies to appear. Insulin autoantibodies typically emerge very early with a peak at the age of 1.5 years, whereas the onset of glutamic acid decarboxylase 65 antibody positivity has a more even distribution, peaking later in childhood. These differences in the timing of appearance suggest that different environmental factors might be involved in the initiation of β-cell autoimmunity beginning either already in infancy or later on. This should be taken into account in studies aimed at identifying environmental factors triggering islet cell-specific autoimmunity and also in the design of prevention trials.
    Expert Review of Endocrinology &amp Metabolism 08/2014;
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    ABSTRACT: Genotyping in closed-tube is commonly performed using PCR amplification and allele specific oligonucleotide probes utilizing fluorescence resonance energy transfer (FRET). Here we introduce a homogenous HLA-DQA1∗05 end-point PCR assay based on switchable lanthanide luminescence probe technology and a simple dried blood sample preparation. The switchable probe technology is based on two non-luminescent oligonucleotide probes, one carrying a non-luminescent lanthanide chelate and the other a light absorbing antenna ligand. Hybridization of the probes in adjacent positions to the target DNA leads to the formation of a highly luminescent lanthanide chelate complex by self-assembly of the reporter molecules. Performance of the HLA-DQA1∗05 assay was evaluated by testing blood samples collected on sample collection cards and prepared by lysing the punched samples (3 mm discs) using alkaline reaction conditions and high temperature. Testing of 147 blood samples yielded 100% correlation to the heterogenous DELFIA-technology based reference assay. Genotyping requires carefully designed probe sequences able to discriminate matched and mismatched target sequences by hybridization. Furthermore, definite genotype discrimination was achieved because inherently non-luminescent switchable probes together with time-resolved measurement mode lead to very low background signal level and, therefore, very high signal differences in average of 54 fold between DQA1∗05 and other alleles.
    Analytical Biochemistry 08/2014; · 2.31 Impact Factor
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    ABSTRACT: Context: In Finland the world-record high incidence of type 1 diabetes has risen steeply over past decades; however, after 2006 the incidence rate has plateaued. We showed earlier, that despite the strong genetic disease component, environmental factors are driving the increasing disease incidence. Objective: Since vitamin D intake has increased considerably in the country since 2003, we analyzed how serum 25-hydroxyvitamin D (25[OH]D) concentration changed over time in healthy children, and the timely relation of these changes to disease incidence. Design, Setting and Participants: The birth cohort of the Finnish Type 1 Diabetes Prediction and Prevention project was used to explore longitudinal changes in serum 25-hydroxyvitamin concentrations. The sampling period was limited to children born during 1994-2004 with serum samples collected during 1998-2006 in Turku area - Southwest Finland (60 °N). Main Outcome Measure: 25(OH)D concentrations were measured every 3-6 months from birth - age range 0.3-12.2 years (387 subjects; 5334 measurements). Results: Serum 25(OH)D concentrations were markedly lower before 2003 than thereafter (69.3±1.0 nmol/L vs. 84.9±1.3 nmol/L, respectively, P < .001) in both genders. The mean difference between the periods was 15.7±1.3 nmol/L (P< .001). Importantly, the frequency of children with low serum 25(OH)D levels (< 50 nmol/L) was reduced to almost half from 2003 (37.3 % versus 69.9 %; P< .001). Similarly, severe vitamin D deficiency (<25 nmol/L) has also decreased (2.7% vs. 7.7%; P = .005). In addition, we detected higher 25(OH)D concentrations in young children (<2 years) as compared to older children, which is explained by higher vitamin D intake in this group. Conclusions: We provide evidence that an increase in circulating concentrations of 25(OH)D shows a delayed temporal association with leveling off of type 1 diabetes incidence in Finland after 2006.
    Journal of Clinical Endocrinology &amp Metabolism 07/2014; · 6.31 Impact Factor

Publication Stats

10k Citations
2,385.92 Total Impact Points

Institutions

  • 2010–2015
    • University of Eastern Finland
      Kuopio, Northern Savo, Finland
    • Diabetes Clinic for Children and Adolescents
      Muenster, North Rhine-Westphalia, Germany
  • 1981–2015
    • University of Turku
      • • Department of Paediatrics
      • • Department of Virology
      • • Aerobiology Unit
      • • Department of Medical Biochemistry and Genetics
      • • Department of Neurology
      Turku, Varsinais-Suomi, Finland
  • 2013
    • VTT Technical Research Centre of Finland
      Esbo, Southern Finland Province, Finland
  • 1996–2013
    • University of Helsinki
      • • The Hospital for Children and Adolescents
      • • Department of Dental Public Health
      • • Department of Nutrition
      • • Department of Pediatrics
      Helsinki, Southern Finland Province, Finland
  • 2012
    • University of Groningen
      • Department of Medical Microbiology
      Groningen, Province of Groningen, Netherlands
  • 2010–2012
    • National Institute for Health and Welfare, Finland
      • • Department of Lifestyle and Participation
      • • Nutrition Unit
      Helsinki, Province of Southern Finland, Finland
  • 2006–2012
    • University of Kuopio
      • Department of Clinical Microbiology
      Kuopio, Eastern Finland Province, Finland
  • 1994–2012
    • University of Tampere
      • • Department of Virology
      • • School of Health Sciences
      • • Paediatric Research Centre
      • • Medical School
      • • Institute of Biomedical Sciences
      Tampere, Western Finland, Finland
  • 2011
    • University of Florida
      • Department of Microbiology and Cell Science
      Gainesville, FL, United States
  • 2008–2011
    • Pirkanmaa Hospital District
      Tammerfors, Province of Western Finland, Finland
  • 1977–2011
    • University of Oulu
      • • Department of Paediatrics
      • • Department of Medical Microbiology
      • • Department of Dermatology and Venereology
      • • Department of Neurology
      Oulu, Oulu, Finland
  • 1998–2010
    • Turku University Hospital
      • Department of Pediatrics
      Turku, Varsinais-Suomi, Finland
    • Kuopio University Hospital
      • Department of Paediatrics
      Kuopio, Province of Eastern Finland, Finland
  • 2006–2008
    • Linköping University
      • Faculty of Health Sciences
      Sweden
  • 2007
    • PerkinElmer
      Waltham, Massachusetts, United States
  • 2005–2007
    • Åbo Akademi University
      Turku, Province of Western Finland, Finland
    • Tampere University Hospital (TAUH)
      Tammerfors, Province of Western Finland, Finland
  • 2003–2006
    • Chumakov Institute of Poliomyelitis and Viral Encephalitides
      Moskva, Moscow, Russia
    • GlaxoSmithKline plc.
      Londinium, England, United Kingdom
  • 1997–2006
    • Turku centre for biotechnology, finland
      Turku, Province of Western Finland, Finland
  • 1983–2006
    • National Public Health Institute
      Helsinki, Southern Finland Province, Finland
  • 1995
    • SickKids
      Toronto, Ontario, Canada
  • 1992
    • 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