Alireza Norouzi; Shohreh Taziki; Ali Najafipasandi; Saeed Mohammadi; Gholamreza Roshandel
Abstract
Background: Natural killer (NK) cells are dichotomously involved in chronic hepatitis B (CHB) infection as principal members of innate immunity. An effective treatment should enhance the antiviral potentials of NK cells and not their immunomodulatory roles. TIM-3 (T-cell immunoglobulin and mucin-containing ...
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Background: Natural killer (NK) cells are dichotomously involved in chronic hepatitis B (CHB) infection as principal members of innate immunity. An effective treatment should enhance the antiviral potentials of NK cells and not their immunomodulatory roles. TIM-3 (T-cell immunoglobulin and mucin-containing domain) is a molecule with an essential role in controlling immune tolerance. TIM-3 demonstrated the highest expression among NK cells of patients with chronic liver disorders. Statins have been reported to attenuate the levels of TIM-3 on NK cells.Objectives: To investigate the frequencies of NK cells, NKT cells, and TIM-3+ population in patients with CHB upon rosuvastatin (RSV) intervention.Methods: Thirty confirmed patients with CHB were randomly assigned into two groups of 15 (receiving 20 mg of RSV or placebo per day) for 12 weeks. We evaluated the percentages of TIM-3+ cells by staining the peripheral blood mononuclear cells (PBMCs) with CD3, CD16, and CD56 markers using flow cytometry.Results: Our findings indicated that RSV administration could increase CD3- CD56+ NK cells (P>0.05) and CD3+ CD16+ CD56+ NKT cells (P<0.05). RSV intervention could reduce the percentages of TIM-3+ cells among NK cells (P<0.01) and NKT cells (P> 0.05) of patients with CHB compared with the placebo group.Conclusions: The increased population of NK and NKT cells and the effective reduction of TIM-3+ cells among patients with CHB delineated that rosuvastatin could be proposed as an appropriate modulator of innate immune response (regarding NK and NKT cells) in favor of enhancing their antiviral activities.
Abolfazl Gheshlaghi; Mohammad Reza Haghshenas; Ali Reza Safarpour; Seyed Younes Hossini; Seyed Ali Malekhosseini; Mohammad Reza Fattahi; Jamal Sarvari
Abstract
Background: Genetic variation in immune regulatory genes might influence the HBV infection outcome. Objective: This study aimed to determinethe association of IL-17A rs2275913 (G197A), IL-17F rs763780 (A7488G), and IL-23R rs10889677 (C2370A) gene polymorphisms, as well as the emerged haplotypes in the ...
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Background: Genetic variation in immune regulatory genes might influence the HBV infection outcome. Objective: This study aimed to determinethe association of IL-17A rs2275913 (G197A), IL-17F rs763780 (A7488G), and IL-23R rs10889677 (C2370A) gene polymorphisms, as well as the emerged haplotypes in the individual infected by HBV and to investigate their association with the infection outcome. Materials and Methods: 300 chronic HBV infections with Cirrhotic/Hepatocellular carcinoma (C/HCC), chronic active (CA), and asymptomatic carrier (AC) and 38 individuals whose infection was spontaneously cleared (SC) were enrolled. Genomic DNA was extracted, and IL-17A/F and IL-23R genotyping were performed by using the PCR-RFLP method. Results: Out of 338 subjects, 238 and 100 were respectively male and /female with a mean age of 47.61±13.41. The frequency of GA genotype (p=0.01) and A alleles (p=0.001) of IL-17A rs2275913 (G197A), as well as the frequency of AA genotype (p=0.014) and A alleles (p=0.018) of IL-17F rs763780 (A7488G) gene locus, was found to be significantly higher in the C/HCC than CA and AC groups. Furthermore, the frequency of GA and AG haplotype in CA individuals was higher than those with C/HCC and AC (p=0.003). Also, the GG haplotype was higher in AC individuals than those with C/HCC (P=0.022), and the AA haplotype was higher in C/HCC individuals than the CA patients (P=0.001). Conclusion: Our findings suggest that A allele and GA genotype at IL-17A rs2275913 (G197A), as well as A allele and AA genotype at IL-17F rs763780 (A7488G) locus, might be associated with increased risk of C/HCC among patients with hepatitis B virus infection.