自然杀伤细胞在慢性乙型肝炎病毒感染中的真正抗病毒能力：支持更早进行抗病毒治疗的论据。
Veritable antiviral capacity of natural killer cells in chronic HBV infection: an argument for an earlier anti-virus treatment.
机构信息
Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, China.
Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, China.
出版信息
J Transl Med. 2017 Oct 31;15(1):220. doi: 10.1186/s12967-017-1318-1.
BACKGROUND
There is limited information on innate immunity, especially natural killer (NK) cell function, in different chronic hepatitis B (CHB) stages. Therefore, we examined whether the clinical staging strategy accurately reflects veritable NK cell immunity.
METHODS
A total of 237 eligible CHB patients and 22 healthy controls were enrolled in our study. Demographic and clinical data were collected, and the CHB phases (immune active-IA, immune tolerant phase-IT, inactive CHB-IC, and grey zone-GZ) were classified according to the latest American Association for the Study of Liver Disease guidelines. Peripheral blood mononuclear cells from patients and healthy controls were tested for NK cell frequency, phenotype and function using flow cytometry.
RESULTS
A significant decrease in activating receptor NKp44 and NKp46 expression and significant increase of exhaustion molecule Tim-3 expression were observed in NK cells from CHB patients. Reduced cytokine secretion and preserved or elevated cytotoxic function were also observed. Patients in the IT group exhibited comparable cytokine secretion and cytolytic capacity as age-matched IA patients. NK cell anti-viral functions were preserved in GZ patients. Some of the NK cell function in patients who were excluded from treatment by the current treatment guidelines was less compromised than patients who qualified for treatment.
CONCLUSION
Our findings provide evidence of veritable NK cell immunity during different natural history phases in treatment-naïve patients with chronic HBV Infection. Chronic HBV infection hindered NK cell function in CHB patients. However, the presumed IT and GZ statuses of CHB patients based on the clinical parameters may not accurately reflect the inner immune status of these patients and should be reconsidered. Some patients excluded from treatment by the current treatment guidelines may be able to be selected as candidates for treatment.
背景
关于不同慢性乙型肝炎（CHB）阶段的固有免疫，尤其是自然杀伤（NK）细胞功能，信息有限。因此，我们研究了临床分期策略是否准确反映了真正的 NK 细胞免疫。
方法
共纳入 237 例符合条件的 CHB 患者和 22 例健康对照者。收集人口统计学和临床数据，并根据最新的美国肝病研究协会指南对 CHB 阶段（免疫激活期-IA、免疫耐受期-IT、非活动 CHB-IC 和灰色区域-GZ）进行分类。使用流式细胞术检测患者和健康对照者外周血单个核细胞中 NK 细胞的频率、表型和功能。
结果
CHB 患者 NK 细胞中观察到激活受体 NKp44 和 NKp46 表达显著下降，耗竭分子 Tim-3 表达显著升高。细胞因子分泌减少，细胞毒性功能保持或升高。IT 组患者的细胞因子分泌和细胞溶解能力与年龄匹配的 IA 患者相当。GZ 患者的 NK 细胞抗病毒功能得到保留。与符合治疗条件的患者相比，一些被当前治疗指南排除治疗的患者的 NK 细胞功能受损程度较小。
结论
我们的研究结果为未经治疗的慢性乙型肝炎感染患者不同自然史阶段的真正 NK 细胞免疫提供了证据。慢性乙型肝炎感染阻碍了 CHB 患者 NK 细胞的功能。然而，基于临床参数推测的 CHB 患者的 IT 和 GZ 状态可能不能准确反映这些患者的内在免疫状态，应重新考虑。一些被当前治疗指南排除治疗的患者可能能够被选为治疗候选者。
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