循环中的囊膜抗体复合物(CAC)驱动肝内补体沉积,为慢性乙型肝炎的亚临床肝脏炎症提供信息

IF 4.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Yijie Tang , Mingzhu Xu , Cong Wang , Min Wu , Lyuyin Hu , Jin Li , Wei Lu , Ye Zheng , Min Zhang , Xizi Jiang , Chuanwu Zhu , Jennifer Audsley , Pisit Tangkijvanich , Anchalee Avihingsanon , Shu Song , Shuangzhe Liu , Sharon R. Lewin , Jacob George , Mark W. Douglas , Yun Ling , Xiaonan Zhang
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引用次数: 0

摘要

慢性乙型肝炎病毒(HBV)感染通常会导致病毒特异性 T 细胞反应失调,阻碍病毒清除。矛盾的是,肝内炎症反应对肝脏组织病理学的影响比对病毒抑制的影响更大,人们普遍认为这种反应是由细胞介导的。然而,体液免疫在这一过程中的参与并没有很好的记录。为了研究 HBV 荚膜-抗体复合物(CACs)在诱发慢性肝脏炎症中可能发挥的作用,我们开发了一种基于微孔板的新型检测方法,用于定量检测血清中的 CACs。CACs 检测法显示出很高的灵敏度和特异性,其读数与 CACs 的分子特征密切相关。一项针对未经治疗的慢性乙型肝炎(CHB)患者的横断面研究显示,CACs 的阳性率为 77%,且与丙氨酸转氨酶(ALT)、肝内炎症和补体沉积密切相关,表明其在肝损伤中的功能性作用。补体活化片段 C4d 与主要白细胞和肌成纤维细胞标记物的多重染色显示,肝周围区域的病变交织在一起,其形态令人联想到 "片状坏死"。在 ALT 水平低于 40 IU/ml 的汇集队列中,仅 CACs 就显示了亚临床肝脏炎症。我们为 CACs 在补体介导的肝内免疫病理中的致病作用提供了确凿证据,而补体介导的肝内免疫病理是导致 CHB 肝损伤的又一机制。对血清中 CACs 的评估补充了目前评估 CHB 相关炎症的临床标记物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Circulating capsid-antibody-complexes (CACs) drive intrahepatic complement deposition and inform subclinical liver inflammation in chronic hepatitis B
Chronic infection with Hepatitis B Virus (HBV) often results in a dysfunctional virus-specific T cell response hampering viral clearance. Paradoxically, intrahepatic inflammatory responses that contribute more to liver histopathology than to viral suppression are commonly observed, which are widely believed to be cell mediated. The involvement of humoral immunity in this process however is not well documented. To investigate the possible roles of HBV Capsid-Antibody Complexes (CACs) in eliciting chronic liver inflammation, we developed a novel microplate-based assay for the quantification of CACs in serum. The CACs assay showed high sensitivity and specificity with its readout closely correlating with the molecular features of CACs. A cross-sectional study on untreated chronic hepatitis B (CHB) patients showed a 77% positive rate for CACs with significant association with alanine transaminase (ALT), intrahepatic inflammation, and complement deposition, suggestive of its functional role in hepatic injury. Multiple staining of complement activation fragment C4d with major leukocyte and myofibroblast markers revealed an intertwined picture in periportal area with a morphology reminiscent of “piecemeal necrosis”. In a pooled cohort with ALT levels lower than 40 IU/ml, CACs alone revealed subclinical liver inflammation. We provide definitive evidence for a causative role for CACs in complement-mediated intrahepatic immunopathology, an additional mechanism contributing to liver damage in CHB. Assessment of CACs in serum complements current clinical markers for assessing CHB associated inflammation.
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来源期刊
Antiviral research
Antiviral research 医学-病毒学
CiteScore
17.10
自引率
3.90%
发文量
157
审稿时长
34 days
期刊介绍: Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.
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