IgE Levels to Ascaris and House Dust Mite Allergens Are Associated With Increased Histone Acetylation at Key Type-2 Immune Genes.

Josefina Zakzuk,Luis Caraballo,Nathalie Acevedo,Hani Harb,Harald Renz,Daniel P Potaczek,Lisa Eick

doi:10.3389/fimmu.2020.00756

Abstract

BackgroundEpigenetic changes in response to allergen exposure are still not well understood. The aim of this study was to evaluate histone acetylation levels in peripheral blood leukocytes from humans naturally infected by intestinal parasites and perennially exposed to house dust mites (HDM).MethodsPeripheral blood mononuclear cells (PBMCs) were isolated by gradient centrifugation from 20 infected and 21 non-infected individuals living in a rural/village in Colombia. Histone 3 acetylation (H3Ac) and histone 4 acetylation (H4Ac) levels were measured in six immune genes previously associated with helminth immunity by chromatin immunoprecipitation (ChIP)-quantitative PCR. Then we analyzed the association between histone acetylation levels with total parasite egg burden and IgE levels.ResultsWe found an inverse correlation between H4Ac levels in the IL13 gene and egg worm burden that remained significant after adjustment by age [−0.20 (−0.32 to −0.09), p < 0.0001]. Moreover, we found significant associations between H4Ac levels in IL4 [0.32 (0.05–0.60), p = 0.02] and CHI3L1 [0.29 (0.08–0.51), p = 0.008] with the IgE levels to Ascaris lumbricoides. In addition, the levels of specific IgE antibodies to HDM were associated with H4Ac levels in the gene TNFSF13B encoding the B cell activating factor (BAFF) [0.51 (0.26–0.76), p < 0.001]. All values are presented as beta (95% CI).ConclusionHistone acetylation levels at key type-2 immune genes in humans were modified by nematode infection and HDM allergens and are associated with the intensity of the IgE response.

Highlights

Epigenetic modifications and DNA methylation, have been associated with increased total IgE levels [1] and increased IgE sensitization to house dust mites (HDM) [2]
Specific IgE levels to Ascaris significantly correlated with fecal egg counts of A. lumbricoides and T. trichiura, thereby the sum of eggs of both helminths per individual was computed as total egg burden and this variable used in all subsequent analyses
This is the first report of association between differences in histone acetylation levels in the Interleukin 13 gene (IL13) gene and parasite egg burden, which is expected because the great importance of IL-13 in helminth immunity [30]

Summary

Introduction

Epigenetic modifications and DNA methylation, have been associated with increased total IgE levels [1] and increased IgE sensitization to house dust mites (HDM) [2]. Allergen exposure induces epigenetic changes in immune cells affecting the inception and maintenance of type-2 skewed immune phenotypes [3]. Histone Acetylation and IgE Levels perennial exposure may explain this observation, the co-exposure with intestinal helminth infection provides a unique opportunity to dissect key molecular events implicated in type 2 immunity [4]. A study in a mice model revealed that chronic helminth infection reprograms T cell differentiation via histone acetylation changes [5], by the addition of acetyl groups to lysine residues (K) at the N-terminal tail of histones. The aim of this study was to evaluate histone acetylation levels in peripheral blood leukocytes from humans naturally infected by intestinal parasites and perennially exposed to house dust mites (HDM)

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