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对乙型肝炎疫苗反应不佳的丙型肝炎治愈患者表现出高的自身反应性免疫特征。

Cured HCV patients with suboptimal hepatitis B vaccine response exhibit high self-reactive immune signatures.

机构信息

Beijing Ditan Hospital, Capital Medical University, Beijing, China.

The Fifth Medical Centre of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.

出版信息

Hepatol Commun. 2023 Jun 28;7(7). doi: 10.1097/HC9.0000000000000197. eCollection 2023 Jul 1.

DOI:10.1097/HC9.0000000000000197
PMID:37378628
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10309501/
Abstract

BACKGROUND AND RATIONALE

Chronic HCV infection induces lasting effects on the immune system despite viral clearance. It is unclear whether certain immune alterations are associated with vaccine responses in cured HCV patients.

APPROACH

Thirteen cured HCV patients received the standard 3-dose hepatitis B vaccine and were followed up at the 0, 1st, 6th, and 7th months (M0, M1, M6, and M7) after the first dose of vaccination. Thirty-three-color and 26-color spectral flow cytometry panels were used for high-dimensional immunophenotyping of the T-cell and B-cell subsets, respectively.

RESULTS

Compared to the healthy controls (HC), 17 of 43 (39.5%) immune cell subsets showed abnormal frequencies in cured HCV patients. Patients with cured HCV were further divided into high responders (HR, n = 6) and nonresponders (NR1, n = 7) based on the levels of hepatitis B surface antibodies at M1. Alterations in cell populations were more significant in NR1. Moreover, we found that high levels of self-reactive immune signatures, including Tregs, TD/CD8, IgD-only memory B, and autoantibodies, were associated with suboptimal hepatitis B vaccine responses.

CONCLUSIONS

Our data suggest that cured HCV patients exhibit persistent perturbations in the adaptive immune system, among which highly self-reactive immune signatures may contribute to a suboptimal hepatitis B vaccine response.

摘要

背景和原理

慢性 HCV 感染可导致病毒清除后免疫系统产生持久影响。目前尚不清楚某些免疫改变是否与已治愈 HCV 患者的疫苗反应有关。

方法

13 名已治愈 HCV 患者接受标准的 3 剂乙型肝炎疫苗接种，并在接种第 1 剂后第 0、1、6 和 7 个月（M0、M1、M6 和 M7）进行随访。使用 33 色和 26 色光谱流式细胞术面板分别对 T 细胞和 B 细胞亚群进行高维免疫表型分析。

结果

与健康对照（HC）相比，在已治愈 HCV 患者中，43 个免疫细胞亚群中有 17 个（39.5%）出现异常频率。根据 M1 时乙型肝炎表面抗体的水平，将已治愈 HCV 患者进一步分为高应答者（HR，n=6）和非应答者（NR1，n=7）。NR1 患者的细胞群改变更为显著。此外，我们发现高水平的自身反应性免疫特征，包括 Tregs、TD/CD8、IgD 仅记忆 B 和自身抗体，与乙型肝炎疫苗应答不佳相关。

结论

我们的数据表明，已治愈 HCV 患者的适应性免疫系统存在持续的紊乱，其中高度自身反应性免疫特征可能导致乙型肝炎疫苗应答不佳。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8522/10309501/2655146e9b75/hc9-7-e00197-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8522/10309501/53caa3e48f6b/hc9-7-e00197-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8522/10309501/797ee0a2c3ed/hc9-7-e00197-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8522/10309501/709056ad45f9/hc9-7-e00197-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8522/10309501/6b1f0d5e12ff/hc9-7-e00197-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8522/10309501/ababb7a2a64a/hc9-7-e00197-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8522/10309501/2655146e9b75/hc9-7-e00197-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8522/10309501/53caa3e48f6b/hc9-7-e00197-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8522/10309501/797ee0a2c3ed/hc9-7-e00197-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8522/10309501/709056ad45f9/hc9-7-e00197-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8522/10309501/6b1f0d5e12ff/hc9-7-e00197-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8522/10309501/ababb7a2a64a/hc9-7-e00197-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8522/10309501/2655146e9b75/hc9-7-e00197-g006.jpg

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