Dataset Information

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

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.

SUBMITTER: Zhou MJ

PROVIDER: S-EPMC10309501 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Zhou Ming-Ju MJ Zhou Ming-Ju MJ Zhang Chao C Fu Yuan-Jie YJ Wang Haiyan H Ji Yingjie Y Huang Xia X Li Lin L Wang Ye Y Qing Song S Shi Yanze Y Shen Lili L Wang You-Yuan YY Li Xiao-Yu XY Li Yuan-Yuan YY Chen Si-Yuan SY Zhen Cheng C Xu Ruonan R Shi Ming M Wang Fu-Sheng FS Cheng Yongqian Y

Hepatology communications 20230628 7

<h4>Background and rationale</h4>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.<h4>Approach</h4>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 pa ...[more]

PMID: 37378628

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Project description:Renal transplantation from hepatitis C (HCV) nucleic acid amplification test-positive (NAAT-positive) donors to uninfected recipients has greatly increased the organ donation pool. However, there is concern for adverse outcomes in these recipients due to dysregulated immunologic activation secondary to active inflammation from acute viremia at the time of transplantation. This includes increased rates of cytomegalovirus (CMV) DNAemia and allograft rejection. In this study, we evaluate transcriptional responses in circulating leukocytes to define the character, timing, and resolution of this immune dysregulation and assess for biomarkers of adverse outcomes in transplant patients. We enrolled 67 renal transplant recipients (30 controls, 37 HCV recipients) and performed RNA sequencing on serial samples from one, 3-, and 6-months post-transplant. CMV DNAemia and allograft rejection outcomes were measured. Least absolute shrinkage and selection operator was utilized to develop gene expression classifiers predictive of clinical outcomes. Acute HCV incited a marked transcriptomic response in circulating leukocytes of renal transplant recipients in the acute post-transplant setting, despite the presence of immunosuppression, with 109 genes significantly differentially expressed compared to controls. These HCV infection-associated genes were reflective of antiviral immune pathways and generally resolved by the 3-month timepoint after sustained viral response (SVR) for HCV. Differential gene expression was also noted from patients who developed CMV DNAemia or allograft rejection compared to those who did not, although transcriptomic classifiers could not accurately predict these outcomes, likely due to sample size and variable time-to-event. Acute HCV infection incites evidence of immune activation and canonical antiviral responses in the human host even in the presence of systemic immunosuppression. After treatment of HCV with antiviral therapy and subsequent aviremia, this immune activation resolves. Changes in gene expression patterns in circulating leukocytes are associated with some clinical outcomes, although larger studies are needed to develop accurate predictive classifiers of these events.

Dataset Information

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

Background and rationale

Approach

Results

Conclusions

Publications

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

Similar Datasets

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