Biology subjects

Ilonen, J.

Publications and source records attributed to Ilonen, J..

5 recordsLinked to original sources

bioRxiv2019

Metabolic Alterations in Human Peripheral Blood Mononuclear Cells Associate with Progression to Islet Autoimmunity and Type 1 Diabetes

Previous metabolomics studies suggest that type 1 diabetes (T1D) is preceded by specific metabolic disturbances. Here we asked whether distinct metabolic patterns occur in peripheral blood mononuclear cells (PBMCs) of children later developing pancreatic {beta}-cell autoimmunity or overt T1D. In a longitudinal cohort setting, PBMC metabolomic analysis was applied in children who either (1) progressed to T1D (PT1D, n=34), (2) seroconverted to [≥]1 islet autoantibody without progressing to T1D (P1Ab, n=27), or (3) remained autoantibody negative during follow-up (CTRL, n=10). During the first year of life, levels of most lipids and polar metabolites were lower in PT1D and P1Ab, versus CTRLs. Pathway overrepresentation analysis suggested alanine, aspartate, glutamate, glycerophospholipid and sphingolipid metabolism were overrepresented in PT1D. Genome-scale metabolic models of PBMCs in T1D progression were developed using available transcriptomics data and constrained with metabolomics data from our study. Metabolic modeling confirmed altered ceramide pathways as specifically associated with T1D progression.

molecular biology↗

bioRxiv2019

Prenatal Exposure to Environmental Chemicals Modulates Serum Phospholipids in Newborn Infants, Increasing Later Risk of Type 1 Diabetes

In the last decade, increasing incidence of type 1 diabetes (T1D) stabilized in Finland, a phenomenon that coincides with tighter regulation of perfluoroalkyl substances (PFAS). Here, we quantified PFAS to examine their effects, during pregnancy, on lipid and immune-related markers of T1D risk in children. In a mother-infant cohort (264 dyads), high PFAS exposure during pregnancy associated with decreased cord serum phospholipids and progression to T1D-associated islet autoantibodies in the offspring. This PFAS-lipid association appears exacerbated by increased human leukocyte antigen-conferred risk of T1D in infants. Exposure to a single PFAS compound or a mixture of organic pollutants in non-obese diabetic mice resulted in a lipid profile characterized by a similar decrease in phospholipids, a marked increase of lithocholic acid, and accelerated insulitis. Our findings suggest that PFAS exposure during pregnancy contributes to risk and pathogenesis of T1D in offspring.

molecular biology↗

bioRxiv2018

Circulating Metabolites in Progression to Islet Autoimmunity and Type 1 Diabetes

Previous studies suggest that metabolic dysregulation precedes the onset of type 1 diabetes (T1D). However, these metabolic disturbances and their specific role in disease initiation remain poorly understood. Here we analysed polar metabolites from 415 longitudinal plasma samples in a prospective cohort of children in three study groups: those who progressed to T1D (PT1D), who seroconverted to one islet autoantibody (Ab) but not to T1D (P1Ab), and Ab-negative controls (CTR). In early infancy, PT1D associated with downregulated amino acids, sugar derivatives and fatty acids, including catabolites of microbial origin, as compared to CTR. Methionine remained persistently upregulated in PT1D as compared to CTR and P1Ab. Appearance of islet autoantibodies associated with decreased glutamic and aspartic acids. Our findings suggest that children who progress to T1D have a unique metabolic profile, which is however altered with the onset of islet autoantibodies. Our findings may assist in early prediction of T1D.

biochemistry↗

bioRxiv2018

Persistent alterations in plasma lipid profiles prior to introduction of gluten in the diet associate with progression to celiac disease

Background and AimsCeliac disease (CD) is a chronic enteropathy characterized by an autoimmune reaction in the small intestine in genetically-susceptible individuals. Gluten is the required environmental trigger of clinical CD, but the underlying causes of the autoimmune reaction remain unknown. Herein, we apply lipidomics to elucidate the early events preceding clinical CD in a prospective study of children observed from birth until diagnosis of CD and subsequent introduction of a gluten-free diet.\n\nMethodsMass spectrometry-based lipidomics profiling was applied to a longitudinal series of 233 plasma samples from the Type 1 Diabetes Prediction and Prevention (DIPP) study, spanning the period between birth and the introduction of a gluten-free diet following CD diagnosis (n=23 CD progressors, n=23 controls matched for gender, HLA risk, period of birth, and age).\n\nResults23 children progressed to CD at a mean age of 4.8 years. They showed increased amounts of triacylglycerols (TGs) of low carbon number and double bond count and a decreased level of phosphatidylcholines by 3 months of age as compared to controls. These differences were exacerbated with age but were not observed at birth. No significant differences were observed in essential (dietary) TGs such as those containing polyunsaturated fatty acids.\n\nConclusionOur findings suggest that abnormal lipid metabolism associated with development of clinical CD may occur prior to the introduction of gluten to the diet. Moreover, our data suggest that the specific TGs found elevated in CD progressors may be due to a host response to compromised intake of essential lipids in the small intestine, requiring de novo lipogenesis.

systems biology↗

bioRxiv2018

Dynamics of Plasma Lipidome in Progression to Islet Autoimmunity and Type 1 Diabetes: Type 1 Diabetes Prediction and Prevention Study (DIPP)

Type 1 diabetes (T1D) is one of the most prevalent autoimmune diseases among children in Western countries. Earlier metabolomics studies suggest that T1D is preceded by dysregulation of lipid metabolism. Here we used a lipidomics approach to analyze molecular lipids in a prospective series of 428 plasma samples from 40 children who progressed to T1D (PT1D), 40 children who developed at least a single islet autoantibody but did not progress to T1D during the follow-up (P1Ab) and 40 matched controls (CTR). Sphingomyelins were found to be persistently downregulated in PT1D when compared to the P1Ab and CTR groups. Triacylglycerols and phosphatidylcholines were mainly downregulated in PT1D as compared to P1Ab at the age of 3 months. Our study suggests that children who progressed to islet autoimmunity or overt T1D are characterized by distinct lipidomic signatures, which may be helpful in the identification of at-risk children before the initiation of autoimmunity.

biochemistry↗