Association of polymorphisms in key Th-17 immune response genes with HBeAg-positive chronic hepatitis B susceptibility and response to PEG-IFNa-2α

Abstract

This study aims to investigate effects of polymorphisms in key Th-17 immune response genes on the susceptibility to HBeAg-positive (HBeAg) chronic hepatitis B (CHB) and response to PEG-IFNa-2α. A total of 139 patients with HBeAg CHB treated with PEG-IFNa-2α and 145 healthy controls were enrolled to explore the association between IL-17A, IL-17F, IL-21 and IL-23R polymorphisms and HBeAg CHB susceptibility, as well as treatment efficacies. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. IL-17A rs4711998 and IL-17F rs763780 may affect susceptibility to HBeAg CHB and response to PEG-IFNa-2α treatment. The T allele of IL-21 rs12508721 may lower HBeAg CHB susceptibility but enhance PEG-IFNa-2α response, and the GA genotype and the A allele of IL-23R rs11209026 may reduce the susceptibility to HBeAg CHB. Th17-related gene polymorphisms were linked to HBeAg CHB susceptibility, and rs4711998, rs763780 and rs12508721 were associated with sustained responses to PEG-IFNa-2α.

Immunity and Fibrogenesis: The Role of Th17/IL-17 Axis in HBV and HCV-induced Chronic Hepatitis and Progression to Cirrhosis

“…At the same time, Th17/IL-17 axis expresses itself, a response to a sustained proinflammatory stimulus ( 51 , 52 ). So, we can understand the broad scope of the elements of this axis on the CVH, predicting outcomes in different points of the disease, from spontaneous healing ( 53 ), response to treatment ( 23 , 54 , 55 ), occurrence of acute decompensations ( 56 ), progression to cirrhosis ( 9 , 28 ), and HCC ( 53 ), including post-transplant recurrence ( 57 ), as detailed in this section.…”

“…Studies in HCV also found the same effect, as shown in a study including 27 HCV-infected patients, in which combined treatment with pegylated IFN-α and ribavirin resulted in a significant decrease in factors related to Th17 (IL-6 and IL-17), Th1 (IFN-α and MIP-1) responses, and profibrotic factors (FGF-b, VEGF); and this impact was principally in responder patients ( 62 ). In another study, Th17-related gene polymorphisms were associated with sustained responses to PEG-IFNa-2α ( 55 ).…”

Exploring the association between Th17 pathway gene polymorphisms and pulmonary tuberculosis

“…Previous studies have demonstrated that the IL-17A concentration increases in TB and is associated with its severity. The IL-17A concentration increased in mouse models and human PBMC cultures in vitro after stimulation with MTB in previous studies ( 24 – 26 ). In another study, the authors found that IL-17F secretion increased in the population with an effective immune response against MTB ( 7 ).…”

“…An important function of IL-23 mediated by the IL-23R complex is to promote the differentiation of T-cells to Th17, thereby increasing the release of other cytokines such as IL-17 and TNF, which are critical for the progression of PTB ( 12 , 33 ). Several studies have confirmed that several SNPs of the IL-23R gene are associated with susceptibility to infectious disease, such as HBeAg-positive chronic hepatitis B ( 24 ). The study by Jiang et al.…”

“…Cytokine secretion is induced by the interaction between different immune cells and bacteria, and IL-17 acts as a pro-inflammatory cytokine by recruiting granulocytes to the sites of infection ( 22 , 23 ). IL-17A and IL-17F, which belong to the IL-17 family, have similar biological functions and can induce target cells to produce multiple inflammatory cytokines, metalloproteinases, and chemokines, resulting in neutrophil recruitment, activation, and exudation to trigger inflammation ( 24 ). Previous studies have demonstrated that the IL-17A concentration increases in TB and is associated with its severity.…”