Epstein-Barr Virus in the Cerebrospinal Fluid and Blood Compartments of Patients With Multiple Sclerosis and Controls.

Background And Objectives: Epstein-Barr virus (EBV) infection is a major risk factor of multiple sclerosis (MS). We examined the presence of EBV DNA in the CSF and blood of patients with MS and controls. We analyzed whether EBV DNA is more common in the CSF of patients with MS than in controls and estimated the proportions of EBV-positive B cells in the CSF and blood.

Cultured lymphocytes' mitochondrial genome integrity is not altered by cladribine.

Cladribine tablets are a treatment for multiple sclerosis with effects on lymphocytes, yet its mode of action has not been fully established. Here, we analyzed the effects of cladribine on mitochondrial DNA integrity in lymphocytes. We treated cultured human T-cell lines (CCRF-CEM and Jurkat) with varying concentrations of cladribine to mimic the slow cell depletion observed in treated patients.

Immune response to a conserved enteroviral epitope of the major capsid VP1 protein is associated with lower risk of cardiovascular disease.

Background: Major cardiac events including myocardial infarction (MI) are associated with viral infections. However, how specific infections contribute to the cardiovascular insults has remained largely unclear.

Methods: We employed next generation phage display mimotope-variation analysis (MVA) to explore the link between antibody-based immune response and severe cardiovascular conditions.

Distribution of perfluoroalkyl acids in fish species from the Baltic Sea and freshwaters in Finland.

Occurrence and distribution of perfluoroalkyl acids (PFAAs), a sub-category of per- and polyfluoroalkyl substances (PFASs), is widespread in the environment. Food, especially fish meat, is a major pathway via which humans are exposed to PFAAs. As fish is an integral part of Nordic diet, therefore, in this study, several fish species, caught in selected Baltic Sea basins and freshwater bodies of Finland, were analysed for PFAAs.

Immunomodulatory Effects of Rhinovirus and Enterovirus Infections During the First Year of Life.

Early childhood infections have been implicated in the development of immune-mediated diseases, such as allergies, asthma, and type 1 diabetes. We set out to investigate the immunomodulatory effects of early viral infections experienced before the age of one year on the peripheral regulatory T cell population (Treg) and circulating cytokines in a birth-cohort study of Estonian and Finnish infants. We show here a temporal association of virus infection with the expression of FOXP3 in regulatory T cells.

Identification of two highly antigenic epitope markers predicting multiple sclerosis in optic neuritis patients.

Background: Optic neuritis (ON) can occur as an isolated episode or will develop to multiple sclerosis (MS) a chronic autoimmune disease. What predicts ON progression to MS remains poorly understood.

Methods: We characterised the antibody epitope repertoire in three independent clinical cohorts (discovery (n = 62), validation (n = 20) and external cohort (n = 421)) using mimotope variation analysis (MVA), a next generation phage display technology to identify epitopes that associate with prognosis of ON.

Maturation of Gut Microbiota and Circulating Regulatory T Cells and Development of IgE Sensitization in Early Life.

Recent studies suggest that the cross-talk between the gut microbiota and human immune system during the first year of life is an important regulator of the later development of atopic diseases. We explored the changes in the gut microbiota, blood regulatory T cells, and atopic sensitization in a birth-cohort of Estonian and Finnish children followed from 3 to 36 months of age. We describe here an infant Treg phenotype characterized by high Treg frequency, the maturation of Treg population characterized by a decrease in their frequency accompanied with an increase in the highly activated Treg cells.

Predisposition to Childhood Otitis Media and Genetic Polymorphisms within the Toll-Like Receptor 4 (TLR4) Locus.

Background: Predisposition to childhood otitis media (OM) has a strong genetic component, with polymorphisms in innate immunity genes suspected to contribute to risk. Studies on several genes have been conducted, but most associations have failed to replicate in independent cohorts.

Methods: We investigated 53 gene polymorphisms in a Finnish cohort of 624 cases and 778 controls.

Th1/Th17 plasticity is a marker of advanced β cell autoimmunity and impaired glucose tolerance in humans.

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.

High-fat meals induce systemic cytokine release without evidence of endotoxemia-mediated cytokine production from circulating monocytes or myeloid dendritic cells.

Aims: Dietary fats have been shown to promote the translocation of bacterial endotoxins from the gut into circulation, which may induce systemic inflammation and modulate the inflammatory response of circulating immune cells. The aim of this study was to determine the effect of the postprandial milieu on inflammation and the inflammatory response of antigen presenting cells in the context of type 1 diabetes (T1D).

Materials And Methods: Eleven patients with T1D and eleven nondiabetic controls were recruited as part of the FinnDiane study and given two fatty meals during 1 day.

Patients with type 1 diabetes show signs of vascular dysfunction in response to multiple high-fat meals.

Background: A high-fat diet promotes postprandial systemic inflammation and metabolic endotoxemia. We investigated the effects of three consecutive high-fat meals on endotoxemia, inflammation, vascular function, and postprandial lipid metabolism in patients with type 1 diabetes.

Methods: Non-diabetic controls (n = 34) and patients with type 1 diabetes (n = 37) were given three high-caloric, fat-containing meals during one day.

Dendritic cells from Crohn's disease patients show aberrant STAT1 and STAT3 signaling.

Abnormalities of dendritic cells (DCs) and STAT proteins have been reported in Crohn's disease (CD). Studies on JAK/STAT signaling in DCs are, however, lacking in CD. We applied a flowcytometric single-cell-based phosphoepitope assay to evaluate STAT1 and STAT3 pathways in DC subsets from CD patients.

Altered phenotype of peripheral blood dendritic cells in pediatric type 1 diabetes.

Objective: Dendritic cells (DCs) are largely responsible for the activation and fine-tuning of T-cell responses. Altered numbers of blood DCs have been reported in type 1 diabetes (T1D). We aimed at characterizing the less well-known phenotypic properties of DCs in T1D.

Expansion of CD4+CD25+FOXP3+ regulatory T cells in infants of mothers with type 1 diabetes.

Background: Reduced risk for type 1 diabetes (T1D) has been reported in the offspring of mothers with T1D when compared with children of affected fathers.

Objective: To evaluate the hypothesis that exposure of the offspring to maternal insulin therapy induces regulatory mechanisms in utero, we compared the FOXP3 expressing regulatory T cells in cord blood (CB) of infants born to mothers with or without T1D.

Subjects And Methods: Cord blood mononuclear cells (CBMCs) from 20 infants with maternal T1D and from 20 infants with an unaffected mother were analyzed for the numbers of CD4+CD25+FOXP3+ cells ex vivo and after in vitro stimulation with human insulin by flow cytometry.

Poor cytokine-induced phosphorylation in chronic myeloid leukemia patients at diagnosis is effectively reversed by tyrosine kinase inhibitor therapy.

Objective: In chronic myeloid leukemia (CML), uncontrolled tyrosine kinase activity of the BCR-ABL1 oncoprotein results in aberrant signaling pathways and increased cell proliferation. Acquired immune tolerance to leukemic antigens further enables tumor cell expansion. Tyrosine kinase inhibitor (TKI) therapy interferes with the immunoregulatory system by targeting off-target kinases both in malignant and nonmalignant cells.

IL-17 immunity in human type 1 diabetes.

Th17 immunity has been shown to regulate autoimmune diabetes in mice. IL-17 neutralization prevented development of diabetes when given postinitiation of insulitis but not earlier, suggesting interference with the effector phase of the disease. Islet-cell Ag-specific Th17 cells converted into IFN-gamma-secreting Th1-like cells and caused diabetes in mice recipients.

Persistence of human parvovirus B19 in human tissues.

Human parvovirus B19 infection causes various clinical symptoms, such as rash, arthropathy, anemias and fetal death, but it can also remain asymptomatic. The arthropathies and anemias can become chronic for several years, not infrequently resembling autoimmune syndromes. B19 replicates only in red blood cell precursors of bone marrow or fetal liver, resulting in high-titred short-lived viremia, but viral DNA is detectable also in cells of several other types.