scholarly journals Identification and Mapping of HBsAg Loss-Related B-Cell Linear Epitopes in Chronic HBV Patients by Peptide Array

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuqin Gu ◽  
Zhipeng Liu ◽  
Li Lin ◽  
Shihong Zhong ◽  
Yanchen Ma ◽  
...  
Keyword(s):  
B Cells ◽  
Hepatitis B ◽  
B Cell ◽  
Antiviral Treatment ◽  
Hbv Infection ◽  
Peptide Array ◽  
Chronic Hbv Infection ◽  
Linear Epitopes ◽  
Chronic Hbv ◽  
P Proteins

Identification of immunogenic targets against hepatitis B virus (HBV)-encoded proteins will provide crucial advances in developing potential antibody therapies. In this study, 63 treatment-naïve patients with chronic HBV infection and 46 patients who achieved hepatitis B surface antigen loss (sAg loss) following antiviral treatment were recruited. Moreover, six patients who transitioned from the hepatitis B e antigen-positive chronic infection phase (eAg+CInf) to the hepatitis phase (eAg+CHep) were enrolled from real-life clinical practice. Additionally, telbivudine-treated eAg+CHep patients and relapsers or responders from an off-treatment cohort were longitudinally studied. The frequencies and function of B cells were assessed by flow cytometry. We devised a peptide array composed of 15-mer overlapping peptides of HBV-encoded surface (S), core (C), and polymerase (P) proteins and performed a screening on B-cell linear epitopes with sera. Naïve B cells and plasmablasts were increased, whereas total memory, activated memory (AM), and atypical memory (AtM) B cells were reduced in sAg- patients compared with sAg+ patients. Importantly, longitudinal observations found that AtM B cells were associated with successful treatment withdrawal. Interestingly, we identified six S-specific dominant epitopes (S33, S34, S45, S76, S78, and S89) and one C-specific dominant epitope (C37) that reacted with the majority of sera from sAg- patients. Of note, more B-cell linear epitopes were detected in CHep patients with alanine aminotransferase (ALT) flares than in nonflare CInf patients, and five B-cell linear epitopes (S4, S5, S10, S11, and S68) were overwhelmingly recognized by ALT flare patients. The recognition rates of epitopes on C and P proteins were significantly increased in CHep patients relative to CInf patients. Strikingly, a statistically significant elevation in the number of positive epitopes was observed when ALT nonflare patients shifted into the flare phase. Moreover, S76 identified at baseline was confirmed to be associated with a complete response after 48 weeks of telbivudine therapy. Taken together, we identified several functional cure-related B-cell linear epitopes of chronic HBV infection, and these epitopes may serve as vaccine candidates to elicit neutralizing antibodies to treat HBV infection.

scholarly journals The Multiple Functions of B Cells in Chronic HBV Infection

2020 ◽  
Vol 11 ◽  
Author(s):  
Ying Cai ◽  
Wenwei Yin
Keyword(s):  
Immune Response ◽  
Chronic Hepatitis ◽  
B Cells ◽  
Hepatitis B ◽  
B Cell ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
Multiple Functions ◽  
Chronic Hbv ◽  
B Cell Subsets

Chronic hepatitis B virus (HBV) infection is one of the main causes of liver diseases, of which the natural history and clinical outcomes are associated with the role of B cells. As humoral immune cells, B cells play a critical role in the process of anti-HBV antibody production. In addition, some studies have also characterized other B cell subsets involved in antigen presentation and regulating the immune response beyond antibody secretion. However, not all B cell subsets play a positive role in the immune response to chronic HBV infection, and various B cell subsets jointly mediate persistent HBV infection, tolerance, and liver damage. Thus, we further sought to elucidate the multiple functions of B cells to gain novel insight into the understanding of chronic hepatitis B (CHB) pathogenesis. We also reviewed the current immunotherapies targeting B cells to explore novel therapeutic interventions for the treatment of chronic HBV infection.

scholarly journals Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection

2020 ◽  
Author(s):  
Xiaoyi Li ◽  
Qifan Zhang ◽  
Wanyue Zhang ◽  
Guofu Ye ◽  
Yanchen Ma ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Hepatitis B ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Hbv Infection ◽  
Follicular Dendritic Cells ◽  
Chronic Hbv Infection ◽  
Chronic Hbv

Abstract Background: The restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. The goal of the present study was to investigate the characteristics and functions of FDCs in chronic HBV infection. Methods: The frequencies of FDCs in peripheral blood, liver, and spleen were measured in patients with chronic HBV infection. Isolated FDCs from splenic tissues of HBV-related liver cirrhosis-induced hypersplenism patients were cultured with autologous intrasplenic CD4 + T cells and CD19 + B cells.Results: We found that patients with chronic HBV infection had a significantly increased frequency of circulating FDCs compared with that of healthy controls. Additionally, the frequency of circulating FDCs was positively correlated with that of intrahepatic and intrasplenic counterparts. Moreover, a positive correlation between the frequency of circulating FDCs and plasmablast and memory B cells, as well as C-X-C motif chemokine receptor type 5 (CXCR5) + CD4 + T cells and CXCR5 + CD8 + T cells was also observed. Notably, in vitro experiments demonstrated that FDCs derived from splenic tissues of chronic HBV patients facilitated interferon-γ and interleukin-21 production from autologous intrasplenic CD4 + T cells and promoted the proliferation of autologous intrasplenic CD19 + B cells. Conclusions: Expanded FDCs in patients with chronic HBV infection may favor the host immune responses against HBV. The identification of this unique population may contribute to a better understanding of the immune regulatory mechanisms and provide a potential immunotherapeutic target in chronic HBV infection.

scholarly journals Benefits and Risks of Antiviral Treatment during Pregnancy in Patients with Chronic Hepatitis B

2021 ◽  
Vol 10 (11) ◽  
pp. 2320
Author(s):  
Yoon Seok Lee ◽  
Soo Min Bang ◽  
Young-Sun Lee
Keyword(s):  
Hepatitis B ◽  
Antiviral Therapy ◽  
Antiviral Treatment ◽  
Hbv Infection ◽  
World Health ◽  
Chronic Hbv Infection ◽  
B Virus ◽  
Chronic Hbv ◽  
Health Organization ◽  
Meta Analyses

Hepatitis B virus (HBV) is a main cause of chronic liver disease worldwide and can lead to severe liver diseases. The World Health Organization has planned to eliminate viral hepatitis, including hepatitis caused by HBV and hepatitis C virus, by 2030. As mother-to-child transmission (MTCT) of HBV is a main cause of chronic HBV infection, MTCT prevention is the main target to reduce the risk of chronic HBV infection and eliminate the disease. Recent clinical trials and meta-analyses found that antiviral therapy could prevent MTCT effectively in mothers with ≥200,000 IU/mL of HBV DNA, in combination with serial vaccination and hepatitis B immune globulin administration in infants. Despite the preventive role of antivirals for MTCT of HBV, there are several concerns regarding antiviral therapy with respect to the safety of the mother and fetus during pregnancy. This review summarizes the benefits and risks of antiviral treatment during pregnancy in women with chronic HBV infection.

scholarly journals Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiaoyi Li ◽  
Qifan Zhang ◽  
Wanyue Zhang ◽  
Guofu Ye ◽  
Yanchen Ma ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Hepatitis B ◽  
Immune Responses ◽  
Hbv Infection ◽  
Follicular Dendritic Cells ◽  
Chronic Hbv Infection ◽  
Chronic Hbv ◽  
Follicular Dendritic

Abstract Background The restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. The goal of the present study was to investigate the characteristics and functions of FDCs in chronic HBV infection. Methods The frequencies of FDCs in peripheral blood, liver, and spleen were measured in patients with chronic HBV infection. Isolated FDCs from splenic tissues of HBV-related liver cirrhosis-induced hypersplenism patients were cultured with autologous intrasplenic CD4+ T cells and CD19+ B cells. Results We observed that patients with chronic HBV infection had a significantly increased frequency of circulating FDCs compared to that of healthy controls. Additionally, the frequency of circulating FDCs was positively correlated with that of intrahepatic and intrasplenic counterparts. Moreover, positive correlations were observed between the frequencies of circulating FDCs and plasmablast and memory B cells, as well as C-X-C motif chemokine receptor type 5 (CXCR5)+CD4+ T cells and CXCR5+CD8+ T cells. Notably, in vitro experimental results demonstrated that FDCs derived from splenic tissues of chronic HBV patients facilitated interferon-γ and interleukin-21 production from autologous intrasplenic CD4+ T cells and promoted the proliferation of autologous intrasplenic CD19+ B cells. Conclusions Expanded FDCs in patients with chronic HBV infection may favor host immune responses against HBV. The identification of this unique population of cell may contribute to a better understanding of the immune regulatory mechanisms associated with chronic HBV infection and provide a potential immunotherapeutic target for this disease.

scholarly journals The Risk of Hepatitis B Reactivation Is Controllable in Patients with Concomitant Hepatitis B Virus Infection during Chimeric Antigen Receptor T-Cell Therapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2913-2913
Author(s):  
Wei Liu ◽  
Rui Lv ◽  
Wenyang Huang ◽  
Hong Liu ◽  
Shuhui Deng ◽  
...  
Keyword(s):  
T Cell ◽  
Hepatitis B ◽  
Cell Therapy ◽  
B Cell ◽  
Hbv Infection ◽  
Hbv Reactivation ◽  
Chronic Hbv Infection ◽  
Car T Cell ◽  
Car T ◽  
Chronic Hbv

Background: Among patients with non-Hodgkin lymphoma (NHL) and concomitant chronic or resolved hepatitis B virus (HBV) infection, HBV reactivation is an identified risk associated with chemotherapy, especially after rituximab-based immunochemotherapy. Chimeric antigen receptor (CAR) T-cell targeting CD19 can also cause B-cell aplasia as seen in patients receiving rituximab, and the risk of HBV reactivation during CAR T-cell therapy is still unknown. We performed a retrospective study to explore the risk of HBV reactivation in patients with concomitant HBV infection who had received anti-CD19 CAR T therapy at our hospital. Methods: Patients with relapse or refractory B-cell lymphoma who were treated with CNCT19 (second-generation anti-CD19 CAR T-cell provided by Juventas) at Blood Disease Hospital were retrospectively analyzed. All patients were screened for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb) at the time of evaluation for CNCT19 therapy, and those with positive HBsAg or positive HBcAb were eligible for this retrospective study. This study was approved by Blood Diseases Hospital Internal Review Board. Results: Between June 2017 and May 2019, 17 patients with relapsed or refractory B-cell lymphoma and concomitant HBV infection who were treated with CNCT19 therapy alone (n=14) or CNCT19 therapy following high-dose chemotherapy and autologous stem cell transplantation (HDT/ASCT, n=3) were included in this study. The median age was 53 years (range: 31-71years), with 53% were male. 6 patients (35%) had chronic HBV infection, defined as positive HBsAg, 11 patients (65%) had resolved HBV infection, defined as negative HBsAg and positive HBcAb. At the time of CNCT19 infusion, HBV DNA levels of all patients were lower than the normal limit (<1000IU/ml). All 6 patients with chronic HBV infection received prophylactic anti-HBV nucleos(t)ide therapy (NAT) of entecavir, 5/11(45%) patients with resolved HBV infection received prophylactic NAT of entecavir or lamivudine, and the other 6/11(55%) patients with resolved HBV infection did not receive any prophylactic anti-HBV therapy. With median follow-up of 8 months (range: 1-24 months) from CNCT19 infusion, including 9 patients who had been followed up for more than 6 months, no HBV reactivation occurred (defined as HBV-DNA level exceeding 1000IU/ml). 6 patients with chronic HBV infection remained on NAT at the time of last follow-up, and among the 5 patients with resolved HBV infection who had received prophylactic NAT during CNCT19 therapy, 1 patient was still on NAT at 3 months after CNCT19 infusion following HDT/ASCT, 4 patients stopped NAT at 1, 2, 6, 6months after CNCT19 infusion, respectively. Cytokine release syndrome (CRS) occurred in 59% of patients and CAR-T-cell-related encephalopathy syndrome (CRES) occurred in 12% of patients, with 2 patients received short term of corticosteroids for grade 4 CRES. Conclusions: Our results showed that CAR T therapy could be safely administered in patients with chronic or resolved HBV infection. Considering the small sample size and the retrospectively analysis, the risk of HBV reactivation and the recommendation for prophylactic anti-HBV NAT during CAR T therapy should be further evaluated in large and prospective studies. Disclosures Lv: Juventas Cell Therapy Ltd.: Employment.

scholarly journals Expanded Circulating Follicular Dendritic Cells Facilitate Immune Responses in Chronic HBV Infection

2020 ◽  
Author(s):  
Xiaoyi Li ◽  
Qifan Zhang ◽  
Wanyue Zhang ◽  
Guofu Ye ◽  
Yanchen Ma ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Hepatitis B ◽  
Immune Responses ◽  
Hbv Infection ◽  
Follicular Dendritic Cells ◽  
Chronic Hbv Infection ◽  
Chronic Hbv ◽  
Follicular Dendritic

Abstract Background: Restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. This study aims to investigate the characteristics and functions of FDCs in chronic HBV infection. Methods: The frequencies of FDCs in peripheral blood, liver, and spleen were measured in patients with chronic HBV infection. Isolated FDCs from splenic tissues of HBV-related liver cirrhosis-induced hypersplenism patients were cultured with autologous intrasplenic CD4+ T cells and CD19+ B cells. Results: We found that patients with chronic HBV infection had a significantly increased frequency of circulating FDCs compared with that of healthy controls. Additionally, the frequency of circulating FDCs was positively correlated with that of intrahepatic and intrasplenic counterparts. Moreover, a positive correlation between the frequency of circulating FDCs and plasmablast and memory B cells, as well as C-X-C motif chemokine receptor type 5 (CXCR5)+CD4+ T cells and CXCR5+CD8+ T cells was also observed. Notably, in vitro experiments demonstrated that FDCs derived from splenic tissues of chronic HBV patients facilitated interferon-γ and interleukin-21 production from autologous intrasplenic CD4+ T cells and promoted the proliferation of autologous intrasplenic CD19+ B cells.Conclusions: Expanded FDCs in patients with chronic HBV infection may favor the host immune responses against HBV. The identification of this unique population may contribute to a better understanding of the immune regulatory mechanisms and provide a potential immunotherapeutic target in chronic HBV infection.

scholarly journals Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection

2020 ◽  
Author(s):  
Xiaoyi Li ◽  
Qifan Zhang ◽  
Wanyue Zhang ◽  
Guofu Ye ◽  
Yanchen Ma ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Hepatitis B ◽  
Immune Responses ◽  
Hbv Infection ◽  
Follicular Dendritic Cells ◽  
Chronic Hbv Infection ◽  
Chronic Hbv ◽  
Follicular Dendritic

Abstract Background: The restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. The goal of the present study was to investigate the characteristics and functions of FDCs in chronic HBV infection. Methods: The frequencies of FDCs in peripheral blood, liver, and spleen were measured in patients with chronic HBV infection. Isolated FDCs from splenic tissues of HBV-related liver cirrhosis-induced hypersplenism patients were cultured with autologous intrasplenic CD4+ T cells and CD19+ B cells. Results: We observed that patients with chronic HBV infection had a significantly increased frequency of circulating FDCs compared to that of healthy controls. Additionally, the frequency of circulating FDCs was positively correlated with that of intrahepatic and intrasplenic counterparts. Moreover, positive correlations were observed between the frequencies of circulating FDCs and plasmablast and memory B cells, as well as C-X-C motif chemokine receptor type 5 (CXCR5)+CD4+ T cells and CXCR5+CD8+ T cells. Notably, in vitro experimental results demonstrated that FDCs derived from splenic tissues of chronic HBV patients facilitated interferon-γ and interleukin-21 production from autologous intrasplenic CD4+ T cells and promoted the proliferation of autologous intrasplenic CD19+ B cells.Conclusions: Expanded FDCs in patients with chronic HBV infection may favor host immune responses against HBV. The identification of this unique population of cell may contribute to a better understanding of the immune regulatory mechanisms associated with chronic HBV infection and provide a potential immunotherapeutic target for this disease.

scholarly journals Hepatitis B Virus Infection in Pregnancy: Immunological Response, Natural Course and Pregnancy Outcomes

2021 ◽  
Vol 10 (13) ◽  
pp. 2926
Author(s):  
Sirinart Sirilert ◽  
Theera Tongsong
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Pregnancy Outcomes ◽  
Natural Course ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
B Virus ◽  
Chronic Hbv ◽  
Adverse Pregnancy ◽  
The Impact

This review aimed to provide an update on the impact of pregnancy on the natural course of hepatitis B virus (HBV) infection and also on the impact of HBV infection on adverse pregnancy outcomes, including mother-to-child transmission (MTCT). For the literature review, original research articles, review articles, and guidelines were narratively reviewed and comprehensively validated. The databases of PubMed, EMBASE, and CINAHL were carefully searched for articles in English on topics related to HBV infection, pregnancy, and vertical transmission from 1960 to May 2021. Immunological changes during pregnancy such as suppression of Th1 response and induction of Th2 immunity lead to an impaired immune reaction to HBV and stimulate viral activity along with the reduction of CD8 T cells to escape immune detection. The impact of pregnancy on the natural course of chronic HBV infection seems to be minimal, while pregnancy can increase morbidity and mortality in the case of advanced HBV hepatitis or cirrhosis. Importantly, hepatitis flare or alanine aminotransferase (ALT) flare can occur during pregnancy and is more common during the postpartum period due to the interaction between HBV and the immune response. Interestingly, the impact of HBV infection on adverse pregnancy outcomes is more serious than ever thought. Updated evidence indicates that pregnancies with chronic HBV infection increase the risk of preterm birth and gestational diabetes, especially in cases of positive hepatitis e antigen (HBeAg).

Sign in / Sign up

Export Citation Format

Share Document