慢性乙型肝炎：肝内淋巴细胞群与病毒抗原之间的相互作用

StephenW

J Viral Hepat. 2019 Feb 9. doi: 10.1111/jvh.13078. [Epub ahead of print]
Chronic Hepatitis B: The interplay between intrahepatic lymphocyte population and viral antigens in relation to liver damage.
Giadans CG1, Ríos DA1, Ameigeiras B2,3, Pietrantonio AM4, Lucatelli NL4, Haddad L5, Mullen E6, Heinrich F3, De Matteo E1, Flichman D7, Valva P1, Preciado MV1.
Author information

1
    Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas (IMIPP- CONICET-GCBA), Laboratorio de Biología Molecular, División Patología, Hospital de Niños Ricardo Gutiérrez, Gallo 1330, C1425EFD, Buenos Aires, Argentina.
2
    Unidad de Hepatología, Hospital Ramos Mejía, Urquiza 609, CP1221, Buenos Aires, Argentina.
3
    Hospital San Antonio, Avenida de La Soberanía s/n (CP: 2840) Gualeguay, provincia de Entre Ríos, Argentina.
4
    División Patología, Hospital Ramos Mejía, Urquiza 609, CP1221, Buenos Aires, Argentina.
5
    Unidad de Hepatología, Hospital Italiano de Buenos Aires, Juan D Perón 4190, C1181ACH, Buenos Aires, Argentina.
6
    División Patología, Hospital Italiano de Buenos Aires, Juan D Perón 4190, C1181ACH, Buenos Aires, Argentina.
7
    Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín, 954, C1113AAD, Buenos Aires, Argentina.

Abstract

In Chronic Hepatitis B (CHB) infection, virus and immune response interplay is thought to be responsible for pathogenesis. Yet, the impact of each immune cell population and viral protein expression in liver damage is still unknown. Our aim was to study the interplay between intrahepatic immune response and viral activity in relation to CHB liver damage. Immunostaining was performed in 29 liver biopsies from untreated CHB patients to characterize liver infiltrate [Th (CD4+), CTL (CD8+), Treg (FoxP3+), Th17 (IL-17A+) and Th1 (Tbet+)] and viral antigen expression (HBsAg and HBcAg). Inflammatory activity and fibrosis were assessed using the HAI and METAVIR scoring system. All studied populations were identified in the portal-periportal (P-P) areas with a CD4+ lymphocyte predominance, while only CD8+ and FoxP3+ cells were observed in the intralobular area. Both P-P CD4+ and intralobular CD8+ cell frequencies were increased among severe hepatitis cases. Concerning HBsAg and HBcAg expression, a mutually exclusive pattern was observed. HBcAg was mainly detected among HBeAg-positive patients and was associated with hepatitis severity and higher frequency of P-P FoxP3+, intralobular CD8+ and FoxP3+ cells. HBsAg was identified among HBeAg-negative cases with less severe hepatitis grade and lower frequency of P-P CD4+ and intralobular FoxP3+ lymphocytes. In conclusion, the HBV antigen profile expression seen during CHB infection may be reflecting different stages of viral replication which impacts the host immune response and liver damage process. While HBcAg might be an inducer of a regulatory microenvironment, the intralobular CTL population seemed to have a key role in hepatitis severity. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.
KEYWORDS:

Chronic hepatitis B; inflammatory infiltrate; liver damage; viral antigen

PMID:
    30739377
DOI:
    10.1111/jvh.13078

StephenW

J病毒肝病。 2019年2月9日doi：10.1111 / jvh.13078。 [印刷前的电子版]
慢性乙型肝炎：肝内淋巴细胞群与病毒抗原之间的相互作用与肝损伤有关。
Giadans CG1，RíosDA1，Ameigeiras B2,3，Pietrantonio AM4，Lucatelli NL4，Haddad L5，Mullen E6，Heinrich F3，De Matteo E1，Flichman D7，Valva P1，Preciado MV1。
作者信息

1
    Instituto Multidisciplinario de InvestigacionesenPatologíasPediátricas（IMIPP-CONICET-GCBA），LaboratoriodeBiologíaMolecular，DivisiónPatología，HospitaldeNiñosRicardoGutiérrez，Gallo 1330，C1425EFD，Buenos Aires，Argentina。
2
    UnidaddeHepatología，医院RamosMejía，Urquiza 609，CP1221，布宜诺斯艾利斯，阿根廷。
3
    医院圣安东尼奥，Avenida deLaSoberaníaS/ n（CP：2840）Gualeguay，provincia deEntreRíos，阿根廷。
4
    DivisiónPatología，医院RamosMejía，Urquiza 609，CP1221，布宜诺斯艾利斯，阿根廷。
五
    UnidaddeHepatología，Hospital Italiano de Buenos Aires，JuanDPerón4190，C1181ACH，Buenos Aires，Argentina。
6
    DivisiónPatología，意大利布宜诺斯艾利斯医院，JuanDPerón4190，C1181ACH，布宜诺斯艾利斯，阿根廷。
7
    CátedradeVirología，Facultad de FarmaciayBioquímica，Universidad de Buenos Aires，Junín，954，C1113AAD，Buenos Aires，Argentina。

抽象

在慢性乙型肝炎（CHB）感染中，病毒和免疫反应相互作用被认为是发病机制的原因。然而，每种免疫细胞群和病毒蛋白表达对肝损伤的影响仍然未知。我们的目的是研究肝内免疫反应与病毒活性之间的相互作用与CHB肝损伤的关系。在来自未治疗的CHB患者的29个肝脏活组织检查中进行免疫染色，以表征肝脏浸润[Th（CD4 +），CTL（CD8 +），Treg（FoxP3 +），Th17（IL-17A +）和Th1（Tbet +）]和病毒抗原表达（HBsAg和核心抗原）。使用HAI和METAVIR评分系统评估炎症活动和纤维化。所有研究的群体在门静脉 - 门静脉（P-P）区域中被鉴定，CD4 +淋巴细胞占优势，而在小叶内区域仅观察到CD8 +和FoxP3 +细胞。重症肝炎病例中P-P CD4 +和小叶内CD8 +细胞频率均增加。关于HBsAg和HBcAg表达，观察到相互排斥的模式。 HBcAg主要在HBeAg阳性患者中检测到，并且与肝炎严重程度和P-P FoxP3 +，小叶内CD8 +和FoxP3 +细胞的频率相关。在HBeAg阴性的病例中发现HBsAg，肝炎等级较轻，P-P CD4 +和小叶内FoxP3 +淋巴细胞频率较低。总之，在CHB感染期间观察到的HBV抗原谱表达可能反映了病毒复制的不同阶段，其影响宿主免疫应答和肝损伤过程。虽然HBcAg可能是调节微环境的诱导物，但是小叶内CTL群体似乎在肝炎严重程度中起关键作用。本文受版权保护。版权所有。

本文受版权保护。版权所有。
关键词：

慢性乙型肝炎;炎性浸润;肝损害;病毒抗原

结论：
    30739377
DOI：
    10.1111 / jvh.13078