Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
Shanghai Institute of Infectious Diseases and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/MOH), Shanghai Medical College, Fudan University, Shanghai, China.
Liver Int. 2023 Feb;43(2):329-339. doi: 10.1111/liv.15489. Epub 2022 Dec 7.
Myeloid-derived suppressor cells (MDSCs) and CD4 regulatory T cells (Tregs) expand during chronic hepatitis B virus (HBV) infection and inhibit antiviral immunity. However, the relationship between antiviral effect and the frequencies of those immune suppressive cells after pegylated interferon α-2a (PegIFNα-2a) therapy is not clearly understood. This study aimed to investigate the contribution of monocytic MDSCs (mMDSCs) and CD4 Tregs to functional cure (HBsAg seroclearance) after PegIFNα-2a therapy and evaluate the effect of PegIFNα-2a therapy on these cells.
Flow cytometry analysis was performed along with longitudinal immune monitoring of 97 hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) patients receiving PegIFNα-2a weekly for 48 weeks.
The frequencies of mMDSCs and CD4 Tregs increased in all HBV patients, and they were higher in the HBsAg persistence group than in the HBsAg seroclearance group. A significant decline in the frequency of mMDSCs was found in patients who realized functional cure after PegIFNα-2a treatment. In contrast, the frequency of CD4 Tregs in both the HBsAg seroclearance and persistence groups significantly increased. Multivariate analyses indicated that the baseline serum HBsAg levels (p < .001) and mMDSCs frequency (p = .027) were independently associated with the HBsAg clearance, and the combined marker (HBsAg plus mMDSCs) displayed the highest specificity (93.1%) than any other markers in predicting HBsAg seroclearance.
These results suggest that a poor response to PegIFNα-2a treatment in CHB patients may be related to the frequencies of immune suppressive cells, while the therapeutic targeting of these cells might be effective in boosting anti-HBV immunity.
髓系来源的抑制性细胞（MDSCs）和 CD4 调节性 T 细胞（Tregs）在慢性乙型肝炎病毒（HBV）感染期间扩增，并抑制抗病毒免疫。然而，在聚乙二醇干扰素 α-2a（PegIFNα-2a）治疗后，抗病毒效果与这些免疫抑制细胞的频率之间的关系尚不清楚。本研究旨在探讨单核细胞来源的 MDSCs（mMDSCs）和 CD4 Tregs 对 PegIFNα-2a 治疗后功能性治愈（HBsAg 血清学清除）的贡献，并评估 PegIFNα-2a 治疗对这些细胞的影响。
对 97 例接受 PegIFNα-2a 每周治疗 48 周的乙型肝炎 e 抗原（HBeAg）阴性慢性乙型肝炎（CHB）患者进行流式细胞术分析和纵向免疫监测。
所有 HBV 患者的 mMDSCs 和 CD4 Tregs 频率均增加，且在 HBsAg 持续组中高于 HBsAg 血清学清除组。在接受 PegIFNα-2a 治疗后实现功能性治愈的患者中，mMDSCs 频率显著下降。相比之下，HBsAg 血清学清除和持续组的 CD4 Tregs 频率均显著增加。多变量分析表明，基线血清 HBsAg 水平（p<0.001）和 mMDSCs 频率（p=0.027）与 HBsAg 清除独立相关，联合标志物（HBsAg 加 mMDSCs）在预测 HBsAg 血清学清除方面的特异性（93.1%）高于任何其他标志物。
这些结果表明，CHB 患者对 PegIFNα-2a 治疗的反应不佳可能与免疫抑制细胞的频率有关，而针对这些细胞的治疗可能有助于增强抗 HBV 免疫。
