Skin tests, T cell responses and self-reported symptoms in children with allergic rhinitis and asthma due to house dust mite allergy

Abstract BACKGROUND: In allergic responses, a distinction is made between an early-phase response, several minutes after allergen exposure, and a late-phase response after several hours. During the late phase, eosinophils and T cells infiltrate the mucosa and play an important role in inflammation. OBJECTIVE: The aim of this study was to examine the relationship between allergen-induced late-phase skin responses and in vitro T cel

Interrelationships between atopic disorders in children

Purpose To study the prevalence and interrelationship between asthma, allergic rhinitis and eczema using data obtained from ISAAC questionnaires. Method The Medline, Pubmed Publisher, EMBASE, Google Scholar and the Cochrane Controlled Clinical Trials Register databases were systematically reviewed to evaluate epidemiological data of children with atopic disorders. To study these interrelationships, a new approach was used. Risk ratios were calculated, describing the risk of having two different atopic disorders when the child is known with one disorder. Results Included were 31 studies, covering a large number of surveyed children (n=1,430,329) in 102 countries. The calculated worldwide prevalence for asthma, eczema and allergic rhinitis is 12.00% (95% CI: 11.99-12.00), 7.88% (95% CI: 7.88-7.89) and 12.66% (95% CI: 12.65-12.67), respectively. The observed prevalence [1.17% (95% CI: 1.17-1.17)] of having all three diseases is 9.8 times higher than could be expected by chance. For children with asthma the calculated risk ratio of having the other two disorders is 5.41 (95% CI: 4.76-6.16), for children with eczema 4.24 (95% CI: 3.75-4.79), and for children with allergic rhinitis 6.20 (95% CI: 5.30-7.27). No studied confounders had a significant influence on these risk ratios. Conclusions Only a minority of children suffers from all three atopic disorders, however this co-occurrence is significantly higher than could be expected by chance and supports a close relationship of these disorders in children. The data of this meta-analysis supports the hypothesis that there could be a fourth distinct group of children with all three disorders. Researchers and clinicians might need to consider these children as a separate group with distinct characteristics regarding severity, causes, treatment or prognosis

Determining the Severity of Atopic Dermatitis in Children Presenting in General Practice: An Easy and Fast Method

Assessment of the severity of atopic dermatitis (AD) is necessary to evaluate the disease process. This study evaluates and validates the TIS in children with AD presenting in general practice. Independent investigators determined the severity of AD using the TIS and the objective SCORAD. The interobserver agreement for the TIS and SCORAD was calculated, as was the correlation between TIS and SCORAD. The mean time to assess the TIS was less than one minute. A moderate-to-good agreement between the observers was found for the TIS (κ = 0.604 or 0.464), or SCORAD (κ = 0.695 or 0.700). There was an excellent correlation between TIS and SCORAD (rs = 0.755–0.839). In conclusion, the TIS is an easy and fast method to score AD. Because of the moderate to good interobserver agreement and the high correlation with the SCORAD, we recommend the TIS to determine the severity of AD in general practice

Evaluation of clinical and immunological responses: A 2-year follow-up study in children with allergic rhinitis due to house dust mite

Background. Allergic rhinitis is a disease with polarization towards Thand a defect of regulatory T cells. Immunological changes have been reported after immunotherapy treatment. However, there is not much known about the natural course of allergic rhinitis with respect to clinical manifestation and the relation with immunological responses. Objective. To evaluate clinical symptoms of allergic rhinitis, in relation to in vivo allergen-specific skin responses and in vitro allergen-specific effector and regulatory T cells determined at baseline and after two years. Methods. From a large trial, 59 children were randomly selected. The following variables were compared: clinical symptoms, allergen skin tests, specific IgE, T-cell proliferation, IL-5, IL-13, IFN-gamma, IL-10, TGF-beta, CD 4 + CD 25 hi cells, and Foxp3 expression. Results. Allergic symptoms had decreased after two years. Whereas skin test reactions correlated between years 0 and 2, there was no change in the size of the reaction. Also, proinflammatory reactions did not change after two years, with a positive correlation between years 0 and 2. No relevant changes were observed with respect to regulatory cells. Conclusion. Whereas, comparable to immunotherapy, allergic complaints decrease, the immunological changes of specific T-cell activity (both effector cells and regulator cells) which are observed after immunotherapy, do not change

Randomized double-blind placebo-controlled trial of sublingual immunotherapy in children with house dust mite allergy in primary care: study design and recruitment

Background. For respiratory allergic disorders in children, sublingual immunotherapy has been developed as an alternative to subcutaneous immunotherapy. Sublingual immunotherapy is more convenient, has a good safety profile and might be an attractive option for use in primary care. A randomized double-blind placebo-controlled study was designed to establish the ef

Age-related accrual of methylomic variability is linked to fundamental ageing mechanisms

Background: Epigenetic change is a hallmark of ageing but its link to ageing mechanisms in humans remains poorly understood. While DNA methylation at many CpG sites closely tracks chronological age, DNA methylation changes relevant to biological age are expected to gradually dissociate from chronological age, mirroring the increased heterogeneity in health status at older ages. Results: Here, we report on the large-scale identification of 6366 age-related variably methylated positions (aVMPs) identified in 3295 whole blood DNA methylation profiles, 2044 of which have a matching RNA-seq gene expression profile. aVMPs are enriched at polycomb repressed regions and, accordingly, methylation at those positions is associated with the expression of genes encoding components of polycomb repressive complex 2 (PRC2) in trans. Further analysis revealed trans-associations for 1816 aVMPs with an additional 854 genes. These trans-associated aVMPs are characterized by either an age-related

Blood lipids influence DNA methylation in circulating cells

Background: Cells can be primed by external stimuli to obtain a long-term epigenetic memory. We hypothesize that long-term exposure to elevated blood lipids can prime circulating immune cells through changes in DNA methylation, a process that may contribute to the development of atherosclerosis. To interrogate the causal relationship between triglyceride, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol levels and genome-wide DNA methylation while excluding confounding and pleiotropy, we perform a stepwise Mendelian randomization analysis in whole blood of 3296 individuals. Results: This analysis shows that differential methylation is the consequence of inter-individual variation in blood lipid levels and not vice versa. Specifically, we observe an effect of triglycerides on DNA methylation at three CpGs, of LDL cholesterol at one CpG, and of HDL cholesterol at two CpGs using multivariable Mendelian randomization. Using RNA-seq data available for a large subset of individuals (N = 2044), DNA methylation of these six CpGs is associated with the expression of CPT1A and SREBF1 (for triglycerides), DHCR24 (for LDL cholesterol) and

Controlling bias and inflation in epigenome- and transcriptome-wide association studies using the empirical null distribution

We show that epigenome- and transcriptome-wide association studies (EWAS and TWAS) are prone to significant inflation and bias of test statistics, an unrecognized phenomenon introducing spurious findings if left unaddressed. Neither GWAS-based methodology nor state-of-the-art confounder adjustment methods completely remove bias and inflation. We propose a Bayesian method to control bias and inflation in EWAS and TWAS based on estimation of the empirical null distribution. Using simulations and real data, we demonstrate that our method maximizes power while properly controlling the false positive rate. We illustrate the utility of our method in large-scale EWAS and TWAS meta-analyses of age and smoking

Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and