Replicated methylation changes associated with eczema herpeticum and allergic response
CLINICAL EPIGENETICS
Authors: Boorgula, Meher Preethi; Taub, Margaret A.; Rafaels, Nicholas; Daya, Michelle; Campbell, Monica; Chavan, Sameer; Shetty, Aniket; Cheadle, Chris; Barkataki, Sangjucta; Fan, Jinshui; David, Gloria; Beaty, Terri H.; Ruczinski, Ingo; Hanifin, Jon; Schneider, Lynda C.; Gallo, Richard L.; Paller, Amy S.; Beck, Lisa A.; Leung, Donald Y.; Mathias, Rasika A.; Barnes, Kathleen C.
Abstract
Background Although epigenetic mechanisms are important risk factors for allergic disease, few studies have evaluated DNA methylation differences associated with atopic dermatitis (AD), and none has focused on AD with eczema herpeticum (ADEH+). We will determine how methylation varies in AD individuals with/without EH and associated traits. We modeled differences in genome-wide DNA methylation in whole blood cells from 90 ADEH+, 83 ADEH-, and 84 non-atopic, healthy control subjects, replicating in 36 ADEH+, 53 ADEH-, and 55 non-atopic healthy control subjects. We adjusted for cell-type composition in our models and used genome-wide and candidate-gene approaches. Results We replicated one CpG which was significantly differentially methylated by severity, with suggestive replication at four others showing differential methylation by phenotype or severity. Not adjusting for eosinophil content, we identified 490 significantly differentially methylated CpGs (ADEH+ vs healthy controls, genome-wide). Many of these associated with severity measures, especially eosinophil count (431/490 sites). Conclusions We identified a CpG in IL4 associated with serum tIgE levels, supporting a role for Th2 immune mediating mechanisms in AD. Changes in eosinophil level, a measure of disease severity, are associated with methylation changes, providing a potential mechanism for phenotypic changes in immune response-related traits.
The levels of 12 cytokines and growth factors in tears: hyperthyreosis vs euthyreosis
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
Authors: Mandic, Jelena Juri; Kozmar, Ana; Kusacic-Kuna, Sanja; Jazbec, Anamarija; Mandic, Kresimir; Mrazovac, Danijela; Vukojevic, Nenad
Abstract
Simultaneous analyses of the contents and ratios of 12 cytokines and growth factors in single samples of human tears were performed, and the results were compared between a group of healthy subjects and a group of patients with Graves' hyperthyreosis (GH) without thyroid-associated orbitopathy (TAO). Determinations and concentration measurements of interleukins (IL-2, IL4, IL-6, IL-8, IL-10, IL-1 alpha, and IL-1 beta) interferon (IFN-gamma), tumor necrosis factor (TNF-alpha), monocyte chemoattractant protein (MCP-1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) were performed with single tear samples from 21 patients with hyperthyreosis and 22 healthy subjects. The analyses were performed using a Randox microchip with an Evidence Biochip Array Analyzer. We found significant differences between the healthy donor group and the hyperthyreosis group in the levels of IL-6, IL-10, VEGF, IL-1 alpha, and MCP-1. The concentration of IL-6 was considerably higher in the hyperthyreosis group, IL-10 was higher in the healthy donor group, and VEGF and MPC-1 were higher in the hyperthyreosis group. The IL-8 and IFN-gamma levels were higher in the hyperthyreosis group. The ratios of all of the cytokines to anti-inflammatory IL-10 were significantly elevated in the hyperthyreosis group. There are clear differences in the levels of cytokines and growth factors in the tears of healthy subjects and patients with GH without TAO. Tear cytokine changes and related dysfunctional tear syndrome (DTS) could be an early sign of occult TAO in Graves' hyperthyreosis patients.