Association between Interleukin-21 and Interleukin-21 receptor gene polymorphisms with susceptibility to chronic hepatitis B virus infection and HBV spontaneous clearance in Iranian population

Shoraka, Shahrzad; Mohebbi, Seyed Reza; Hosseini, Seyed Masoud; Razavi, Armin Hosseini; Hatami, Yasin; Sharifian, Afsaneh; Rostami-Nejad, Mohammad; Aghdaei, Hamid Asadzadeh; Zali, Mohammad Reza

doi:10.1016/j.micpath.2019.01.008

Cited by 10 publications

(9 citation statements)

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“…On the basis of serological markers, CHB can be divided into four different clinical phases [14], [15], [23]- [27]. Host genetic background and immune response have significant roles in HBV outcome [52], [53]. Many studies have shown the relationship between progression of CHB infection and host immune responses [34], [54].…”

Section: Resultsmentioning

confidence: 99%

Evaluation of IL-17A and IL-17F Gene Expression in Peripheral Blood Mononuclear Cells in Different Clinical Stages of Chronic Hepatitis B Infection in an Iranian Population

Kolagar

Mohebbi

Ashrafi

et al. 2020

MST

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Hepatitis B virus (HBV) infection is one of the main causes of liver damage, which can also lead to chronic hepatitis B (CHB) infection. More than 240 million individuals worldwide are chronic carriers of HBV. Among individuals with CHB who are untreated, approximately 15%-40% will progress to liver cirrhosis or cancer. The interactions between HBV and host immune response play significant roles in the progression of CHB. CHB can be generally divided into four different clinical phases: immune tolerance (IT), immune clearance, inactive carrier, and Hepatitis B surface antigen (HBsAg)negative reactivation phase (ENEG). Many studies showed that interleukins play important roles in anti-viral immunity and pathogenesis of chronic hepatitis. However, the relations between clinical phases of CHB and host immune transcriptome remain unclear. In this study, we aimed to investigate the expression of interleukin-17A (IL-17A) and IL-17F genes in the peripheral blood mononuclear cells (PBMCs) of patients with CHB through different clinical stages. Results were compared with the control group, which comprised individuals with no history of pre-existing medical conditions. This case-control study was carried out on 32 patients with CHB as the case group and 32 healthy individuals as the control group. According to clinical data, CHB cases were divided into two groups: active (n = 22) and inactive (n = 11). PBMC samples were obtained from all groups. After total RNA extraction and cDNA synthesis, real-time PCR was used to determine IL-17A and IL-17F expression levels. The results were analyzed by REST software, SPSS, and GraphPad Prism. The IL-17A and IL-17F gene expression levels were observed to be significantly higher in the CHB group than in the control group (IL-17A: P = 0.0013; IL-17F: P = 0.0103). The active phase group (including IT, clearance, and reactivation samples) significantly increased in comparison with the inactive phase (IL-17A: P = 0.000; IL-17F: P = 0.000). The study suggests that IL-17A and IL-17F do not only activate inflammation but are also involved in HBV-related disease progression and chronicity. Thus, mRNA levels of IL-17A and IL-17F could be used as a biomarker to diagnose CHB infection and distinguish between the active CHB phase from the inactive phase. Abstrak Evaluasi Ekspresi Gen IL-17A dan IL-17F di dalam Sel-Sel Inti Tunggal Darah Tepi pada Tahapan-tahapan Klinis yang Berbeda dari Infeksi Hepatitis B Kronis pada Suatu Populasi Orang Iran. Infeksi virus hepatitis B (HBV) merupakan salah satu dari penyebab utama kerusakan hati, yang dapat juga menyebabkan infeksi hepatitis B kronis (CHB). Lebih dari 240 juta individu di seluruh dunia merupakan pembawa kronis HBV. Di antara individu-individu dengan CHB yang tidak diobati, hampir 15%-40% akan berkembang menjadi sirosis hati atau kanker. Interaksi antara HBV dan respons imun inang memegang peran yang signifikan dalam perkembangan CHB. CHB pada umumnya dapat dibagi menjadi empat fase klinik yang berbeda: tolerasi imun (IT), pembersihan imun, pemba...

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Section: Resultsmentioning

confidence: 99%

Evaluation of IL-17A and IL-17F Gene Expression in Peripheral Blood Mononuclear Cells in Different Clinical Stages of Chronic Hepatitis B Infection in an Iranian Population

Kolagar

Mohebbi

Ashrafi

et al. 2020

MST

Self Cite

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“…The level of expression of IL-21 in the peripheral blood of PTB patients also significantly decreases ( 35 ). Previous studies have analyzed the association between IL-21 gene variation and the risk of infectious diseases ( 37 , 38 ), but its role in PTB has not been explored. This is the first study to analyze the associations between IL-21 gene rs907715 and rs2055979 polymorphisms and PTB; however, no significant association was found.…”

Section: Discussionmentioning

confidence: 99%

Exploring the association between Th17 pathway gene polymorphisms and pulmonary tuberculosis

Wang

Huang

et al. 2022

Front. Immunol.

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Th17 cells play a key role in immunity against Mycobacterium tuberculosis (MTB), and this study aimed to explore the association of Th17 pathway gene polymorphisms with pulmonary tuberculosis (PTB) susceptibility in a Chinese population. A total of 10 single nucleotide polymorphisms in Th17 pathway genes (IL-17A gene rs2275913, rs3748067, rs8193036, rs3819024, IL-17F gene rs7741835, rs763780, IL-21 gene rs907715, rs2055979, IL-23R gene rs11805303, and rs7518660) were genotyped in 456 PTB patients and 466 controls using SNPscan technique. The IL-23R rs11805303 CC genotype, C allele frequencies were significantly lower in PTB patients than in controls, and the rs11805303 variant was significantly associated with the reduced risk of PTB in a recessive model. There were no significant associations between IL-17A, IL-17F, and IL-21 gene variations and PTB risk. In IL-17A gene, rs2275913, rs3748067, and rs3819024 variants were associated with drug resistance in PTB patients. In IL-17F gene, rs7741835 variant affected drug resistance, and rs763780 variant was associated with hypoproteinemia in PTB patients. In addition, the lower frequencies of the TT genotype, T allele of rs2055979 were found in PTB patients with drug-induced liver injury. Haplotype analysis showed that IL-23R CG haplotype frequency was significantly lower in PTB patients than in controls, while the TG haplotype frequency was higher. In conclusion, IL-23R rs11805303 polymorphism may contribute to the genetic underpinnings of PTB in the Chinese population, and the IL-17A, IL-17F, and IL-21 genetic variations are associated with several clinical manifestations of PTB patients.

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“…Interleukin-21 (IL-21) plays an important role in both innate and acquired immune responses, and its expression is significantly increased in a variety of viral infections. The specific receptor IL-21R is produced and localized on the surface of T and B cells and natural killer (NK) cells, which plays a key role in the proliferation and differentiation of these immune effector cells (Shoraka et al 2019 ). IL-21 can also increase the number of helper (CD4 + ) T cells and germinal center B cells, thus increasing the immunity of the body (Zhang et al 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Lactobacillus plantarum surface-displayed ASFV (p54) with porcine IL-21 generally stimulates protective immune responses in mice

et al. 2021

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African classical swine fever virus (ASFV) has spread seriously around the world and has dealt with a heavy blow to the pig breeding industry due to the lack of vaccines. In this study, we produced recombinant Lactobacillus plantarum (L. plantarum) expressing an ASFV p54 and porcine IL-21 (pIL-21) fusion protein and evaluated the immune effect of NC8-pSIP409-pgsA'-p54-pIL-21 in a mouse model. First, we verified that the ASFV p54 protein and p54-pIL-21 fusion protein were anchored on the surface of L. plantarum NC8 by flow cytometry, immunofluorescence and Western blotting. Then, the results were verified by flow cytometry, ELISA and MTT assays. Mouse-specific humoral immunity and mucosal and T cell-mediated immune responses were induced by recombinant L. plantarum. The results of feeding mice recombinant L. plantarum showed that the levels of serum IgG and mucosal secreted IgA (SIgA), the number of CD4 and CD8 T cells, and the expression of IFN-γ in CD4 and CD8 T cells increased significantly, and lymphocyte proliferation occurred under stimulation with the ASFV p54 protein. Our data lay a foundation for the development of oral vaccines against ASFV in the future.

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Association between Interleukin-21 and Interleukin-21 receptor gene polymorphisms with susceptibility to chronic hepatitis B virus infection and HBV spontaneous clearance in Iranian population

Cited by 10 publications

References 50 publications

Evaluation of IL-17A and IL-17F Gene Expression in Peripheral Blood Mononuclear Cells in Different Clinical Stages of Chronic Hepatitis B Infection in an Iranian Population

Evaluation of IL-17A and IL-17F Gene Expression in Peripheral Blood Mononuclear Cells in Different Clinical Stages of Chronic Hepatitis B Infection in an Iranian Population

Exploring the association between Th17 pathway gene polymorphisms and pulmonary tuberculosis

Lactobacillus plantarum surface-displayed ASFV (p54) with porcine IL-21 generally stimulates protective immune responses in mice

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