General and Specific Genetic Polymorphism of Cytokines-Related Gene in AITD

Chen Xiaoheng,Mei Yizhou,Ding Zhiguo,Wang Xin,Li Lu,Li Huilong,Hu Rui,He Bei

doi:10.1155/2017/3916395

Chen Xiaoheng, Mei Yizhou + Show 6 more

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https://doi.org/10.1155/2017/3916395

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Abstract

Autoimmune thyroid disease (AITD) shows the highest incidence among organ-specific autoimmune diseases and is the most common thyroid disease in humans, including Graves' disease (GD) and Hashimoto's thyroiditis (HT). The susceptibility to autoimmune diseases is affected by increased autoantibody levels, susceptibility gene polymorphisms, environmental factors, and psychological factors, but the pathogenesis remains unclear. Various cytokines and related genes encoding them play important roles in the development and progression of AITD. CD152, an expression product of the CTLA-4 gene, downregulates T cell activation. The A/A genotype polymorphism in the CT60 locus may reduce the production of thyroid autoantibodies. The C1858T polymorphism of the PTNP22 gene reduces the expression of its encoded LYP, which increases the risk of GD and HT. GD is an organ-specific autoimmune disease involving increased secretion of thyroid hormone, whereas HT may be associated with the destruction of thyroid gland tissue and hypothyroidism. These two diseases exhibit similar pathogenesis but opposite trends in the clinical manifestations. In this review, we focus on the structure and function of these cytokines and related genes in AITD, as well as the association of polymorphisms with susceptibility to GD and HT, and attempt to describe their differences in pathogenesis and clinical manifestations.

Highlights

Autoimmune thyroid disease (AITD) accounts for 90% of all thyroid diseases, mainly including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). Both diseases show similar pathological features and pathogenesis: (1) thyroid symmetric hyperplasia and thyroid lymphocyte infiltration; (2) varying number of thyroid antibodies detected in the serum; (3) family inheritance; (4) occurring in the same thyroid at the same time; and (5) GD and HT in the same patient which can be exhibited as phase transformation [1]
In a study by Bossowski [30, 31], CD152 expression on peripheral blood T cells increased in GD patients, which may be related to defective CD152 function caused by CTLA-4 gene polymorphisms
Shi et al [86] found that the frequency of DQA1∗0301 DQB1∗0201 in Canadian patients with HT was significantly increased by PCR-sequencespecific oligonucleotide, and the susceptibility of HT might be through DQA1∗0301/DR4 DQB1∗0201/DR3

Summary

Introduction

Autoimmune thyroid disease (AITD) accounts for 90% of all thyroid diseases, mainly including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). Both diseases show similar pathological features and pathogenesis: (1) thyroid symmetric hyperplasia and thyroid lymphocyte infiltration; (2) varying number of thyroid antibodies detected in the serum; (3) family inheritance; (4) occurring in the same thyroid at the same time; and (5) GD and HT in the same patient which can be exhibited as phase transformation [1]. Low thyroid parenchyma lymphocyte infiltration and simultaneously present thyrotropin receptor antibodies induce thyroid follicular cell proliferation, which eventually develops into hyperthyroidism. Abnormal expression of a variety of cytokines such as HLA, CD152, LYP, FcRL3, CD40, and their genes will inhibit autoimmune tolerance [6]

Cytokines and Cytokine-Related Genes in AITD

Genetic Polymorphism of Cytokine-Related Genes Associated with Both GD and HT

Specific Genetic Polymorphism of Cytokine-Related Gene Associated with GD

Specific Genetic Polymorphism of Cytokine-Related Gene Associated with HT

Findings

Conclusion and Prospects