Association of Toll-Like Cell Receptors TLR2 (p.Arg753GLN) and TLR4 (p.Asp299GLY) Polymorphisms with Indicators of General and Local Immunity in Patients with Atopic Dermatitis.

Yury A Tyurin,Irina D Reshetnikova,Nikolay N Kalinin,Anton F Shamsutdinov,Alsou A Sharifullina

doi:10.1155/2017/8493545

Abstract

A whole group of polymorphisms of genes involved in the formation of the epidermal barrier, immune responses, and their regulation is important in the formation of atopic phenotype. The purpose of the study is to determine the relationship of polymorphisms of genes of Toll-like receptors TLR2 and TLR4 with clinical and immunological parameters in atopic dermatitis patients in a “case-control” study. Polymorphisms of genes TLR2 (p.Arg753Gln) and TLR4 (Asp299Gly) were detected by PCR. Parameters of the state of innate and adaptive immunity were assessed by the level of local production of sIgA, cytokine profile of blood serum for IL-4, IL-10, and IFN-γ. Biological samples from 50 people with allergic pathology, aged 4.5 to 35 years, and 100 healthy individuals (controls) were analyzed. Observed dysregulation of cytokine production (IL-4, IL-10) in patients with heterozygous polymorphic genotypes probably reflects an imbalance of Th1/Th2/Th17 regulation of immune system response in these individuals.

Highlights

Human allergic diseases are considered today a medical issue of global significance which leads to a considerable reduction in the quality of life and public health
The distribution of alleles and genotypes of the TLR2 and TLR4 receptor polymorphisms in the tested groups was consistent with the Hardy–Weinberg–Castle law and did not deviate from the equilibrium
We found that the G/G homozygous genotype was 1,17 times less frequent in the group of patients with atopic dermatitis than it was in the group of healthy individuals, whereas the G/A∗ genotype was found to be 3,3 times more frequent in the first group than in the second

Summary

Introduction

Human allergic diseases are considered today a medical issue of global significance which leads to a considerable reduction in the quality of life and public health. Extensive studies of the last two decades on the pathogenesis of allergic diseases suggest that they are associated with a number of genetic and environmental factors and with the interaction of these factors, all of which lead to a quite complex pathogenesis and considerable difficulties for a rational therapy. Molecular and genetic studies of the last 20 years have shown that there are several hundreds of gene mutations involved in the development of an atopic phenotype [1]. In the case of atopic dermatitis, for example, there were identified significant associations with gene polymorphism regarding those genes involved in the development of the epidermal barrier, the appearance of immune responses, and their regulation [1]. Important are the studies on associations between different polymorphic forms of genes controlling innate and adaptive immune responses in the pathogenesis of allergic diseases. It has been shown that TLR2 and TLR4 cell receptors participate in the development of innate and adaptive immune responses to lipoteichoic acids forming the cell wall of Gram-positive bacteria and to viral proteins and LPS of Journal of Immunology Research

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