An Exploratory Pilot Study of Genetic Marker for IgE-Mediated Allergic Diseases with Expressions of FcεR1α and Cε.

En-Chih Liao,Ching-Yun Chang,Sheng-Jie Yu,Chia-Wei Hsieh,Sui-Chu Yin,Jaw-Ji Tsai

doi:10.3390/ijms16059504

Abstract

The high affinity immunoglobulin E (IgE) receptor-FcεR1 is mainly expressed on the surface of effector cells. Cross-linking of IgE Abs bound to FcεR1 by multi-valent antigens can induce the activation of these cells and the secretion of inflammatory mediators. Since FcεR1 plays a central role in the induction and maintenance of allergic responses, this study aimed to investigate the association of FcεR1 with the allergic phenotype of Cε expression and cytokine and histamine release from peripheral leukocytes. Peripheral leukocytes from 67 allergic and 50 non-allergic subjects were used for genotyping analysis. Peripheral mononuclear cells (PBMCs) were used for Cε expression and ELISpot analysis, while polymorphonuclear cells (PMNs) were used for histamine release. The association between genotype polymorphism of the FcεR1α promoter region (rs2427827 and rs2251746) and allergic features of Cε expression and histamine were analyzed, and their effects on leukocytes function were compared with wild type. The genotype polymorphisms of FcεR1α promoter region with CT and TT in rs2427827 and TC in rs2251746 were significantly higher in allergic patients than in non-allergic controls. Patients with single nucleotide polymorphism (SNP) of FcεR1α promoter region had high levels of total IgE, mite-specific Der p 2 (Group 2 allergen of Dermatophagoides pteronyssinus)-specific IgE and IgE secretion B cells. The mRNA expression of FcεR1α was significantly increased after Der p2 stimulation in PBMCs with SNPs of the FcεR1α promoter region. Despite the increased Cε mRNA expression in PBMCs and histamine release from PMNs and the up-regulated mRNA expression of interleukin (IL)-6 and IL-8 secretions after Der p2 stimulation, there was no statistically significant difference between SNPs of the FcεR1α promoter region and the wild type. SNPs of FcεR1α promoter region were associated with IgE expression, IgE producing B cells, and increased Der p2-induced FcεR1α mRNA expression. These SNPs may be used as a disease marker for IgE-mediated allergic inflammation caused by Dermatophagoides pteronyssinus.

Highlights

Immunoglobulin E (IgE) is most frequently recognized for its role in type-I hypersensitivity reaction.During the IgE-mediated response, IgE binds with a high-affinity IgE receptor consisting of a tetramer of a ligand-binding α chain (FcεR1α), a signal-augmenting β, and a signal-transducing γ chain dimer.The receptor is abundantly expressed on the surface of mast cells and basophils, and is thought to be involved in allergic inflammation of the asthmatic airway
Because high total serum IgE levels are closely correlated with the clinical expression and severity of asthma and allergy, IgE is thought to play a key role in the pathogenesis of allergic diseases [1,2]
This study reveals that the secretions of IL-6 and IL-8 from PBMCs of patients with or without single nucleotide polymorphism (SNP) of the FcεR1α promoter region are significantly increased after Der p2

Summary

Introduction

The receptor is abundantly expressed on the surface of mast cells and basophils, and is thought to be involved in allergic inflammation of the asthmatic airway. Because high total serum IgE levels are closely correlated with the clinical expression and severity of asthma and allergy, IgE is thought to play a key role in the pathogenesis of allergic diseases [1,2]. The regulation of serum IgE production is largely influenced by familial determinants [3,4]. Chen et al found that a common variant in FcεR1α was associated with total serum IgE levels in cord blood or blood samples from birth up to the first six years of life, and this was independent of environmental endotoxin exposure from house dust samples [6]

Objectives

Methods

Results

Conclusion