Folate intake during pregnancy may affect the regulation of DNA methylation during fetal development. The genomic regions in the offspring that may be sensitive to folate exposure during in utero development have not been characterized. Using genome-scale profiling, we investigated DNA methylation in 2 immune cell types (CD4(+) and antigen-presenting cells) isolated from neonatal cord blood, selected on the basis of in utero folate exposure. High-folate (HF; n=11) and low-folate (LF; n=12) groups were selected from opposite extremes of maternal serum folate levels measured in the last trimester of pregnancy. A comparison of these groups revealed differential methylation at 7 regions across the genome. By far, the biggest effect observed was hypomethylation of a 923 bp region 3 kb upstream of the ZFP57 transcript, a regulator of DNA methylation during development, observed in both cell types. Levels of H3/H4 acetylation at ZFP57 promoter and ZFP57 mRNA expression were higher in CD4(+) cells in the HF group relative to the LF group. Hypomethylation at this region was replicated in an independent sample set. These data suggest that exposure to folate has effects on the regulation of DNA methylation during fetal development, and this may be important for health and disease.

The discovery of immunoglobulin E (IgE) was a breakthrough in the field of Allergy and Immunology. Our understanding of mechanisms of allergic reactions and the role of IgE in these disorders has paralleled to the discovery of treatment modalities for patients with allergy. Apart from allergic diseases, IgE is involved in pathogenesis of other disorders. Much controversy exists about the control of total IgE (tIgE) levels and allergen-specific IgE (sIgE) profiles in allergic individuals. This review aims at giving a comprehensive overview of IgE molecule and discussing the issues related to its importance in clinical setting.

While immunodeficiency of immaturity of the neonate has been considered important as the basis for unusual susceptibility to infection, it has also been recognized that the ability to progress from an immature Th2 cytokine predominance to a Th1 profile has relevance in determining whether children will develop allergy, providing an opportunity for epigenetic regulation through environmental pressures. However, this notion remains relatively unexplored. Here, we present evidence that there are two major control points to explain the immunodeficiency in cord blood (CB) T-cells, a deficiency in interleukin (IL)-12 (IL-12) producing and IL-10 overproducing accessory cells, leading to a decreased interferon γ (IFNγ) synthesis and the other, an intrinsic defect in T-cell protein kinase C (PKC) ζ (PKCζ) expression. An important finding was that human CB T-cells rendered deficient in PKCζ, by shRNA knockdown, develop into low tumour necrosis factor α (TNFα) and IFNγ but increased IL-13 producing cells. Interestingly, we found that the increase in PKCζ levels in CB T-cells caused by prenatal supplementation with fish oil correlated with modifications of histone acetylation at the PKCζ gene (PRKCZ) promoter. The data demonstrate that PKCζ expression regulates the maturation of neonatal T-cells into specific functional phenotypes and that environmental influences may work via PKCζ to regulate these phenotypes and disease susceptibility.

Objectives: The use of latex gloves has increased by several folds in the recent past due to concerns about blood-borne infections. Data from Asian countries with regard to latex allergy is scarce. The objective of this study was to determine the prevalence and risk factors of latex allergy among healthcare workers in a tertiary hospital in Sri Lanka. Material and Methods: A cross-sectional survey was carried out among different categories of employees in the hospital. A self-administered questionnaire was used to collect data related to latex allergy. Results: A total of 524 employees was recruited and 62% responded to the questionnaire. Among them 49.2% wore gloves for more than 1 hour a day. Symptoms suggestive of latex allergy were reported by 53 (16.3%) subjects. A considerable proportion (11.4%) of workers had been suffering from latex allergy for more than 5 years. Nurses accounted for the highest prevalence for any job category, while the unit with the highest rate was the surgical ward. Duration in the service (OR = 1.006, P = 0.048) and wearing gloves for more than one hour a day (OR = 3.292, P = 0.004) were significant risk factors for latex allergy, but not atopy or family history of atopy. Seven employees noticed that they developed food allergy after assuming duties as healthcare personnel. Conclusions: Prevalence of latex allergy is high among healthcare workers in this study population. Environmental factors rather than genetic predisposition play the major role in the development of this condition.

Introduction: Chronic inflammatory diseases including allergies and asthma are the result of complex interactions between genes and environmental factors. Epigenetic mechanisms comprise a set of biochemical reactions that regulate gene expression. In order to understand the cause-effect relationship between environmental exposures and disease development, methods capable of assessing epigenetic regulation (also) in large cohorts are needed. Methods: For this purpose, we developed and evaluated a miniaturized chromatin immunoprecipitation (ChIP) assay allowing for a cost-effective assessment of histone acetylation of candidate genes in a quantitative fashion. This method was then applied to assess H3 and H4 histone acetylation changes in cord blood (CB) samples from an established cohort of Australian children exposed in the fetal period to either very low or very high levels of maternal folate. Results: Our ChIP assay was validated for a minimum requirement of 1 × 10⁵ target cells (e.g. CD4+ T cells). Very high levels of maternal folate were significantly associated with increased H3/H4 acetylation at GATA3 and/or IL9 promoter regions in CD4+ T cells in CB. Conclusion: We developed a ChIP method allowing reliable assessment of H3/H4 acetylation using 1 × 10⁵ cells only. Practical application of this assay demonstrated an association between high maternal folate exposure and increased histone acetylation, corresponding to a more transcriptionally permissive chromatin status in the promoter regions of some Th2-related genes.