Wang Jiayi, Lu Jiajie, Zhou Chen, Du Lingyao, Tang Hong
Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, P. R. China.
Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, P. R. China.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2023 Feb 25;40(1):79-86. doi: 10.7507/1001-5515.202301014.
This study aims to clarify host factors of IFN treatment in the treatment of chronic hepatitis B (CHB) patients by screening the differentially expressed genes of IFN pathway CHB patients with different response to interferon (IFN) therapy. Three cases were randomly selected in IFN-responding CHB patients (Rs), non-responding CHB patients (NRs) and healthy participants, respectively. The human type I IFN response RT profiler PCR array was used to detect the expression levels of IFN-related genes in peripheral blood monocytes (PBMCs) from healthy participants and CHB patients before and after Peg-IFN-α 2a treatment. The results showed that more differentially expressed genes appeared in Rs group than NRs group after IFN treatment. Comparing with healthy participants, IFNG, IL7R, IRF1, and IRF8 were downregulated in both Rs and NRs group before IFN treatment; CXCL10, IFIT1, and IFITM1 were upregulated in the Rs; IL13RA1 and IFI35 were upregulated in the NRs, while IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1, and ADAR were downregulated. The expression of IL15, IFI35 and IFI44 was downregulated by 4.09 ( = 10.58, < 0.001), 5.59 ( = 3.37, = 0.028) and 10.83 ( = 2.8, = 0.049) fold in the Rs group compared with the NRs group, respectively. In conclusion, IFN-response-related gene array is able to evaluate IFN treatment response by detecting IFN-related genes levels in PBMC. High expression of CXCL10, IFIT1 and IFITM1 before treatment may suggest satisfied IFN efficacy, while high expression of IL13RA1, IL15, IFI35 and IFI44 molecules and low expression of IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1 and ADAR molecules may be associated with poor IFN efficacy.
本研究旨在通过筛选对干扰素(IFN)治疗有不同反应的慢性乙型肝炎(CHB)患者IFN通路的差异表达基因,阐明IFN治疗CHB患者的宿主因素。分别在IFN应答CHB患者(Rs)、无应答CHB患者(NRs)和健康参与者中随机选取3例。使用人类I型IFN反应RT Profiler PCR阵列检测健康参与者和CHB患者在聚乙二醇化干扰素-α 2a治疗前后外周血单核细胞(PBMC)中IFN相关基因的表达水平。结果显示,IFN治疗后Rs组出现的差异表达基因比NRs组更多。与健康参与者相比,IFNG、IL7R、IRF1和IRF8在IFN治疗前的Rs组和NRs组中均下调;CXCL10、IFIT1和IFITM1在Rs组中上调;IL13RA1和IFI35在NRs组中上调,而IFRD2、IL11RA、IL4R、IRF3、IRF4、PYHIN1和ADAR下调。与NRs组相比,Rs组中IL15、IFI35和IFI44的表达分别下调了4.09倍(F = 10.58,P < 0.001)、5.59倍(F = 3.37,P = 0.028)和10.83倍(F = 2.8,P = 0.049)。总之,IFN反应相关基因阵列能够通过检测PBMC中IFN相关基因水平来评估IFN治疗反应。治疗前CXCL10、IFIT1和IFITM1的高表达可能提示IFN疗效良好,而IL13RA1、IL15、IFI35和IFI44分子的高表达以及IFRD2、IL11RA、IL4R、IRF3、IRF4、PYHIN1和ADAR分子的低表达可能与IFN疗效不佳有关。