A5024634851- Diabetes and associated disorders
- Pancreatic function and diabetes
- Diabetes Management and Research
- Celiac Disease Research and Management
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunodeficiency and Autoimmune Disorders
- Viral Infections and Immunology Research
- Gut microbiota and health
- Diet, Metabolism, and Disease
- Viral gastroenteritis research and epidemiology
- Digestive system and related health
- Pediatric health and respiratory diseases
- Per- and polyfluoroalkyl substances research
- Adrenal Hormones and Disorders
- Advanced Glycation End Products research
- Infant Nutrition and Health
- Probiotics and Fermented Foods
- Birth, Development, and Health
- Clostridium difficile and Clostridium perfringens research
- Urinary Tract Infections Management
- Hormonal Regulation and Hypertension
- COVID-19 Clinical Research Studies
- Vitamin D Research Studies
- vaccines and immunoinformatics approaches
Helsinki Children's Hospital
2024
Helsinki University Hospital
2015-2024
University of Helsinki
2015-2024
Helsinki Art Museum
2021
Children's Hospital at Westmead
2013
Tampere University Hospital
2008
Tampere University
2008
Institute for Molecular Medicine Finland
1997-2003
University of Turku
2000
City of Helsinki
1990
The gut microbial community is dynamic during the first 3 years of life, before stabilizing to an adult-like state. However, little known about impact environmental factors on developing human microbiome. We report a longitudinal study microbiome based DNA sequence analysis monthly stool samples and clinical information from 39 children, half whom received multiple courses antibiotics life. Whereas most children born by vaginal delivery was dominated Bacteroides species, four cesarean...
The role of the intestinal microbiota as a regulator autoimmune diabetes in animal models is well-established, but data on human type 1 are tentative and based studies including only few study subjects. To exclude secondary effects HLA risk genotype gut microbiota, we compared composition children with at least two diabetes-associated autoantibodies (n = 18) autoantibody-negative matched for age, sex, early feeding history, using pyrosequencing. Principal component analysis indicated that...
Significance Type 1 diabetes (T1D) is a major autoimmune disease with increasing incidence in recent years. In this study, we found that the intestinal viromes of cases were less diverse than those controls. We identified eukaryotic viruses and bacteriophage contigs are associated presence or absence autoimmunity. These provide targets for future mechanistic studies to differentiate causal incidental associations between virome protection against development T1D.
OBJECTIVE To test whether weaning to a bovine insulin-free cow's milk formula (CMF) reduces type 1 diabetes mellitus-associated autoantibodies in children at genetic risk. DESIGN Randomized, double-blind pilot trial (Finnish Dietary Intervention Trial for the Prevention of Type Diabetes [FINDIA]). SETTING Three pediatric hospitals Finland from May 15, 2002, November 22, 2005. PARTICIPANTS A total 1113 infants with HLA-conferred susceptibility were randomly assigned receive study infant...
The Islet Autoantibody Standardization Program (IASP) aims to improve the performance of immunoassays measuring type 1 diabetes (T1D)-associated autoantibodies and concordance results among laboratories. IASP organizes international interlaboratory assay comparison studies in which blinded serum samples are distributed participating laboratories, followed by centralized collection analysis results, providing participants with an unbiased comparative assessment. In this report, we describe...
To determine the frequency of newly diagnosed diabetic children with first- and second-degree relatives affected by type 1 diabetes to characterize effects this positive family history on clinical markers, signs β-cell autoimmunity, HLA genotype in index case.Children (n = 1,488) under 15 years age were included a cross-sectional study from Finnish Pediatric Diabetes Register. Data metabolic decompensation at diagnosis collected using questionnaire. Antibodies autoantigens (islet cell...
Recent evidence from serum metabolomics indicates that specific metabolic disturbances precede β-cell autoimmunity in humans and can be used to identify those children who subsequently progress type 1 diabetes. The mechanisms behind these are unknown. Here we show the specificity of pre-autoimmune changes, as indicated by their conservation a murine model We performed study non-obese prediabetic (NOD) mice which recapitulated design human derived states longitudinal lipidomics data. female...
Abstract Upregulation of IL-17 immunity and detrimental effects on human islets have been implicated in type 1 diabetes. In animal models, the plasticity Th1/Th17 cells contributes to development autoimmune this study, we demonstrate that upregulation pathway peripheral blood are markers advanced β cell autoimmunity impaired function Activated Th17 was observed late stage preclinical diabetes children with glucose tolerance, but not early autoimmunity. We found an increased ratio IFN-γ/IL-17...
The gut microbiota is crucial in the regulation of bile acid (BA) metabolism. However, not much known about BAs during progression to type 1 diabetes (T1D). Here, we analyzed serum and stool longitudinal samples collected at 3, 6, 12, 18, 24, 36 months age from children who developed a single islet autoantibody (AAb) (P1Ab; n = 23) or multiple AAbs (P2Ab; 13) controls (CTRs; 38) remained AAb negative. We also microbiome subgroup these children. Factor analysis showed that had strongest...
OBJECTIVE Previous findings suggest that there are age-related endotypes of type 1 diabetes with different underlying etiopathological mechanisms in those diagnosed at age <7 years compared ≥13 years. We set out to explore whether variation demographic, clinical, autoimmune, and genetic characteristics children adolescents newly support the existence these proposed endotypes. RESEARCH DESIGN AND METHODS used data from Finnish Pediatric Diabetes Register analyze 6,015 between 2003...
There is growing evidence suggesting that chemical exposure alters gut microbiota composition. However, not much known about the impact of per- and polyfluoroalkyl substances (PFAS) on microbial community. Here, in a mother-infant study, we set out to identify bacterial species associate with before (maternal) after (maternal, infant) birth. Paired serum stool samples were collected from dyads (n = 30) longitudinal setting. PFAS quantified maternal examine their associations compositions...
Abstract Aims/hypothesis Infection with coxsackie B viruses (CVBs) can cause diseases ranging from mild common cold-type symptoms to severe life-threatening conditions. CVB infections are considered be prime candidates for environmental triggers of type 1 diabetes. This, together the significant disease burden acute and their association chronic other than diabetes, has prompted development human vaccines. The current study evaluated safety immunogenicity first vaccine designed against CVBs...
We set out to define the characteristics of humoral autoimmunity against ZnT8 in children and adolescents with newly diagnosed T1D relation age metabolic status at diagnosis, human leucocyte antigen (HLA) genotype family history T1D.A total 2115 subjects <15 years were analysed for antibodies zinc transporter 8, ICA, GADA, IAA, IA-2A, HLA DR-DQ genotype, blood pH, plasma glucose β-hydroxybutyrate concentrations. Their was also recorded.Zinc 8 (ZnT8A) detected 63% cases. ZnT8A positivity...
The relationship between patterns of islet autoantibodies at diagnosis and specificity the first autoantibody initiation autoimmunity was analyzed with aim identifying informative primary autoantibodies.Information about a single seroconversion data were available for 128 children participating in follow-up cohort Finnish Type 1 Diabetes Prediction Prevention (DIPP) study. Autoantibody genotyping results also obtained from Pediatric Register (FPDR).Insulin (IAA) most common antibodies (N =...
Background The etiology of type 1 diabetes (T1D) is largely unknown. Infections and microbial exposures are believed to play a role in the pathogenesis development islet autoimmunity genetically susceptible individuals. Objective To assess relationships between early childhood infections, autoimmunity, progression T1D predisposed children. Methods Children with human leukocyte antigen (HLA)-conferred disease susceptibility (N=790; 51.5% males) from Finland (n = 386), Estonia 322), Russian...
Mesencephalic astrocyte-derived neurotrophic factor (MANF) was recently shown to be essential for the survival and proliferation of pancreatic β-cells in mice, where deletion MANF resulted diabetes. The current study aimed at determining whether concentration circulating is associated with clinical manifestation human type 1 diabetes (T1D). expression T1D or levels serum have not been previously studied. We developed an enzyme-linked immunosorbent assay (ELISA) measured concentrations from...
The appearance of type 1 diabetes (T1D)-associated autoantibodies is the first and only measurable parameter to predict progression toward T1D in genetically susceptible individuals. However, indicate an active autoimmune reaction, wherein immune tolerance already broken. Therefore, there a clear urgent need for new biomarkers that onset reaction preceding autoantibody positivity or reflect progressive β-cell destruction. Here we report mRNA sequencing–based analysis 306 samples including...
Although gut bacterial dysbiosis is recognized as a regulator of beta-cell autoimmunity, no data available on fungal in the children at risk type 1 diabetes (T1D). We hypothesized that co-occurrence and contributes to intestinal inflammation autoimmune destruction insulin-producing beta-cells T1D. Fecal blood samples were collected from 26 tested positive for least one diabetes-associated autoantibody (IAA, GADA, IA-2A or ICA) matched autoantibody-negative with HLA-conferred susceptibility...
Abstract Narcolepsy type 1 (NT1) is a chronic neurological disorder having strong association with HLA-DQB1*0602, thereby suggesting an immunological origin. Increased risk of NT1 has been reported among children or adolescents vaccinated AS03 adjuvant-supplemented pandemic H1N1 influenza A vaccine, Pandemrix. Here we show that pediatric Pandemrix-associated patients have enhanced T-cell immunity against the viral epitopes, neuraminidase 175–189 (NA ) and nucleoprotein 214–228 (NP ), but...
Summary In this study we aim to describe the characteristics of non-diabetic organ donors with circulating diabetes-associated autoantibodies collected within Nordic Network for Islet Transplantation. One thousand and thirty have been screened in Uppsala antibodies against glutamic acid decarboxylase (GADA) islet antigen-2 (IA-2A). The 32 that tested positive GADA (3·3% all donors) were studied more detail, together matched controls. Mean age among autoantibody-positive was 52·6 (range...
In previous studies, the risk of developing familial type 1 diabetes has been reported to be more than two times higher in offspring affected fathers those mothers. We tested hypothesis that index children with an father may have a aggressive disease process at diagnosis other first-degree relatives. A cross-sectional, observational study was performed using Finnish Pediatric Diabetes Register. Clinical and metabolic characteristics, beta cell autoantibodies HLA class II genetics were...
Abstract Insulin‐dependent (type 1) diabetes is characterized by progressive destruction of insulin‐producing β cells probably autoreactive T lymphocytes. Viral infections, especially those caused coxsackieviruses, are postulated to play a role in the pathogenesis disease humans. One mechanism which viral infections could initiate or accelerate diabetogenic processes “molecular mimicry,” induction antiviral immune responses cross‐reacting with epitopes β‐cell autoantigens. Tyrosine...