New Year, New Hay Fever Season, and New Role for Epigenetics in Allergies
Itching of the eyes and nose, nasal congestion, sneezing, and runny nose are some symptoms of Allergic Rhinitis, better known as hay fever or seasonal allergies, which affects ~30% of people worldwide. In a recent PLOS Genetics publication, scientists from Sweden and the US investigated genome-wide DNA methylation and gene expression changes in CD4+ T-cells from patients with seasonal allergic rhinitis (SAR) and compared them to cells from a healthy control group. Furthermore, the researchers analyzed CD4+ T-cells from the same patient when they were symptom-free (outside of the pollen season) and when they exhibited allergy symptoms. They found that DNA methylation levels, but not changes in gene expression, were significantly different in samples from allergic patients compared to healthy control subjects.
The authors first looked at the genome-wide DNA methylation and gene expression differences in CD4+ T-cells isolated from SAR patients and healthy controls in an in vitro experiment. In this experiment, they isolated peripheral blood mononuclear cells (PBMCs) from the two different groups (allergic and healthy) outside of the pollen season and challenged the cells in vitro with either grass pollen extract or diluent (PBS). After seven days of exposure, the scientists isolated the CD4+ T-cells and investigated them with regards to gene expression and DNA methylation. The researchers found that the DNA methylation levels clearly separated the CD4+ T-cells from allergic patients and healthy controls. In contrast, the scientists found no significant differences between the two groups with regards to gene expression changes.
In a next step, the scientists investigated the genome-wide DNA methylation and gene expression changes from in vivo samples. In these experiments, the researches isolated the CD4+ T-cells from blood collected from SAR patients and healthy controls both during and outside of the pollen season. The DNA and RNA were isolated simultaneously from each sample, and the genome-wide gene expression and DNA methylation patterns were investigated. The authors analyzed the data using unsupervised hierarchical clustering of samples by mRNA expression profile, and were not able to separate samples by disease state. However, DNA methylation analysis was able to separate allergic patients from healthy controls. Furthermore, the separation based on DNA methylation differences was possible both during and outside of the pollen season. Due to the fact that the DNA methylation differences between the disease and healthy group for the 1,000 most significantly altered CpG sites showed small changes of just +/- 10%, the authors picked five CpG loci and validated the changes in DNA methylation using pyrosequencing.
Because of the low percentage change of DNA methylation between the groups, the scientists suggested that it may not be the DNA methylation in a given type of cell that is changing in response to allergens in allergic patients, but rather that the observed differences are based on the changes in the proportion of different types of T-cells present. Therefore, alterations in the CD4+ T-cell population may be a general feature of several immune diseases and DNA methylation might be potentially a promising tool to stratify many different immune diseases. Because DNA methylation changes are generally reversible, it may be possible in the future to treat allergies and other immune disorders with epigenetic therapeutics.
Nestor CE, Barrenäs F, Wang H, Lentini A, Zhang H, Bruhn S, Jörnsten R, Langston MA, Rogers G, Gustafsson M, & Benson M (2014). DNA Methylation Changes Separate Allergic Patients from Healthy Controls and May Reflect Altered CD4(+) T-Cell Population Structure. PLoS genetics, 10 (1) PMID: 24391521