Intrahepatic transcriptomics reveals gene signatures in chronic hepatitis B patients responded to interferon therapy.
Intrahepatic transcriptomics reveals gene signatures in chronic hepatitis B patients responded to interferon therapy.
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DOI：
10.1080/22221751.2022.2100831
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发表时间：
2022-12
影响因子：
13.2
通讯作者：
中科院分区：
文献类型：
--
作者：
慢性B型肝炎病毒（HBV）感染仍然是世界范围内的重大公共卫生负担。α-干扰素（IFNα）是目前批准的治疗慢性B型肝炎（CH B）的两种疗法之一，为了探讨IFNα治疗应答的机制，我们采用mRNA-seq技术研究了21例CH B患者基线和治疗24周时肝内基因表达谱。数据分析表明，PegIFNα治疗显著诱导抗病毒应答。HBV DNA丢失和HBeAg或HBsAg血清转换的应答者表现出更高的倍数变化和更多的上调干扰素刺激基因（ISG）。有趣的是，在其基线活检样品中的应答者中观察到某些ISG的较低表达水平。在HBeAg+患者中，无应答者的基线HBeAg水平相对高于应答者。更重要的是，HBeAg阴性患者的HBsAg丢失率高于HBeAg阳性患者。尽管HBeAg-患者的ISG倍数变化大于HBeAg+患者，但HBeAg+应答者的ISG上调超过HBeAg-应答者。值得注意的是，PegIFNα治疗增加了单核细胞和肥大细胞浸润，但减少了应答者和非应答者中的CD 8 T细胞和M1巨噬细胞浸润，而B细胞浸润仅在应答者中增加。此外，共表达分析确定核糖体蛋白作为抗病毒反应的关键球员。这些数据还表明IFNα可能影响与内质网相关的病毒抗原的产生。总的来说，本研究中的肝内转录组分析丰富了我们对IFN介导的抗病毒作用在CHB患者中的理解，并为改善IFNα治疗的潜在策略的开发提供了新的见解。
Chronic hepatitis B virus (HBV) infection remains a substantial public health burden worldwide. Alpha-interferon (IFNα) is one of the two currently approved therapies for chronic hepatitis B (CHB), to explore the mechanisms underlying IFNα treatment response, we investigated baseline and 24-week on-treatment intrahepatic gene expression profiles in 21 CHB patients by mRNA-seq. The data analyses demonstrated that PegIFNα treatment significantly induced antiviral responses. Responders who achieved HBV DNA loss and HBeAg or HBsAg seroconversion displayed higher fold change and larger number of up-regulated interferon-stimulated genes (ISGs). Interestingly, lower expression levels of certain ISGs were observed in responders in their baseline biopsy samples. In HBeAg+ patients, non-responders had relative higher baseline HBeAg levels than responders. More importantly, HBeAg− patients showed higher HBsAg loss rate than HBeAg+ patients. Although a greater fold change of ISGs was observed in HBeAg− patients than HBeAg+ patients, upregulation of ISGs in HBeAg+ responders exceeded HBeAg− responders. Notably, PegIFNα treatment increased monocyte and mast cell infiltration, but decreased CD8 T cell and M1 macrophage infiltration in both responders and non-responders, while B cell infiltration was increased only in responders. Moreover, co-expression analysis identified ribosomal proteins as critical players in antiviral response. The data also indicate that IFNα may influence the production of viral antigens associated with endoplasmic reticulum. Collectively, the intrahepatic transcriptome analyses in this study enriched our understanding of IFN-mediated antiviral effects in CHB patients and provided novel insights into the development of potential strategies to improve IFNα therapy.
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影响因子：
6.7
作者：
Bility MT;Cheng L;Zhang Z;Luan Y;Li F;Chi L;Zhang L;Tu Z;Gao Y;Fu Y;Niu J;Wang F;Su L
通讯作者：
Su L
影响因子：
6.7
作者：
Fletcher SP;Chin DJ;Gruenbaum L;Bitter H;Rasmussen E;Ravindran P;Swinney DC;Birzele F;Schmucki R;Lorenz SH;Kopetzki E;Carter J;Triyatni M;Thampi LM;Yang J;AlDeghaither D;Murreddu MG;Cote P;Menne S
通讯作者：
Menne S
影响因子：
3.8
作者：
Amiot, Laurence;Vu, Nicolas;Samson, Michel
通讯作者：
Samson, Michel
DOI：
10.1172/jci121960
发表时间：
2018-10-01
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Burton AR;Pallett LJ;McCoy LE;Suveizdyte K;Amin OE;Swadling L;Alberts E;Davidson BR;Kennedy PT;Gill US;Mauri C;Blair PA;Pelletier N;Maini MK
通讯作者：
Maini MK
影响因子：
6.7
作者：
Gill US;Peppa D;Micco L;Singh HD;Carey I;Foster GR;Maini MK;Kennedy PT
通讯作者：
Kennedy PT