Remodeling of B-Cell Subsets in Blood during Pegylated IFNα-2a Therapy in Patients with Chronic Hepatitis B Infection

Aspord, Caroline; Costa, Juliana Bruder; Jacob, Marie‐Christine; Dufeu‐Duchesne, Tania; Bertucci, Inga; Pouget, Noelle; Brevot-Lutton, Ophelie; Zoulim, Fabien; Bourlière, Marc; Plumas, Joël; Leroy, Vincent

doi:10.1371/journal.pone.0156200

Cited by 9 publications

(5 citation statements)

References 38 publications

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“…[100][101][102] Pegylated-IFN-α treatment might exert the immunomodulatory effect by remodeling B cell compartments, which was correlated with a sustained increase in sCD30 levels and decrease of plasma HBsAg. 103,104 TLR agonists and checkpoint inhibitors are an emerging treatment strategy for CHB patients. TLR7 is highly expressed on B cells and has been proven to inhibit antibody production.…”

Section: Novel Chb Treatment Strategies Targeting B Cellsmentioning

confidence: 99%

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B Cell-mediated Humoral Immunity in Chronic Hepatitis B Infection

Yang¹,

Yin²,

Issa³

et al. 2021

Journal of Clinical and Translational Hepatology

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B cell-mediated humoral immunity plays a vital role in viral infections, including chronic hepatitis B virus (HBV) infection, which remains a critical global public health issue. Despite hepatitis B surface antigen-specific antibodies are essential to eliminate viral infections, the reduced immune functional capacity of B cells was identified, which was also correlated with chronic hepatitis B (CHB) progression. In addition to B cells, T follicular helper (Tfh) cells, which assist B cells to produce antibodies, might also be involved in the process of anti-HBVspecific antibody production. Here, we provide a comprehensive review of the role of various subsets of B cells and Tfh cells during CHB progression and discuss current novel treatment strategies aimed at restoring humoral immunity. Understanding the mechanism of dysregulated B cells and Tfh cells will facilitate the ultimate functional cure of CHB patients.

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Section: Novel Chb Treatment Strategies Targeting B Cellsmentioning

confidence: 99%

“… 100 – 102 Pegylated-IFN-α treatment might exert the immunomodulatory effect by remodeling B cell compartments, which was correlated with a sustained increase in sCD30 levels and decrease of plasma HBsAg. 103 , 104 …”

Section: Introductionmentioning

confidence: 99%

B Cell-mediated Humoral Immunity in Chronic Hepatitis B Infection

Yang¹,

Yin²,

Issa³

et al. 2021

Journal of Clinical and Translational Hepatology

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“…In HBeAg-negative chronic patients, the absolute number of HBV-specific CD8 + T cells was strikingly reduced on PEG-IFNα-2b therapy whereas numbers of CD56 bright NK cell increased, showing differential boosting of innate and adaptive antiviral responses ( 4 , 16 ).Also in HBeAg-negative chronic patients, PEG-IFNα-2b therapy showed a major impact on peripheral B cell subsets and a complete remodeling of the B cell compartment ( 17 ). In HBeAg-positive chronic patients, PEG-IFNα-2b has shown to induce a distinct and rapid up-regulation of IFN signaling pathway that coincided with the up-regulation of the frequency of proliferating NK and activated total CD8 + T cells in the first 14 days of IFN-α treatment ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

Immunomodulation Induced During Interferon-α Therapy Impairs the Anti-HBV Immune Response Through CD24+CD38hi B Cells

Wang

Shen

et al. 2020

Front. Immunol.

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Type I interferon is widely used for antiviral therapy, yet has yielded disappointing results toward chronic HBV infection. Here we identify that PEG-IFNα-2b therapy toward persistent infection in humans is a double-edged sword of both immunostimulation and immunomodulation. Our studies of this randomised trial showed persistent PEG-IFNα-2b therapy induced large number of CD24+CD38hi B cells and launched a CD24+CD38hi B cells centered immunosuppressive response, including downregulating functions of T cells and NK cells. Patients with low induced CD24+CD38hi B cells have achieved an improved therapeutic effect. Specifically, using the anti-CD24 antibody to deplete CD24+CD38hi B cells without harming other B cell subsets suggest a promising strategy to improve the therapeutic effects. Our findings show that PEG-IFNα-2b therapy toward persistent infection constitutes an immunomodulation effect, and strategies to identifying the molecular basis for the antiviral versus immunomodulatory effects of PEG-IFNα-2b to selectively manipulate these opposing activities provide an opportunity to ameliorate anti-virus immunity and control viral infection.

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“…Except for the proven effect of PegIFNα on natural killer cells and T cells ( 55 ), B cells are greatly important in this process as well ( 72 ). PegIFNα treatment may play an immunomodulatory role through remodeling the B cell compartments, which is related to continously increased sCD30 levels and decreased plasma HBsAg ( 73 ). HBcAb is an important indicator of host humoral immune response.…”

Section: Anti-viral Therapy and Host Immune Responsementioning

confidence: 99%

Hepatitis B functional cure and immune response

2022

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Hepatitis B virus (HBV) is a hepatotropic virus, which damage to hepatocytes is not direct, but through the immune system. HBV specific CD4+ T cells can induce HBV specific B cells and CD8+ T cells. HBV specific B cells produce antibodies to control HBV infection, while HBV specific CD8+ T cells destroy infected hepatocytes. One of the reasons for the chronicity of HBV infection is that it cannot effectively activate adoptive immunity and the function of virus specific immune cells is exhausted. Among them, virus antigens (including HBV surface antigen, e antigen, core antigen, etc.) can inhibit the function of immune cells and induce immune tolerance. Long term nucleos(t)ide analogues (NAs) treatment and inactive HBsAg carriers with low HBsAg level may “wake up” immune cells with abnormal function due to the decrease of viral antigen level in blood and liver, and the specific immune function of HBV will recover to a certain extent, thus becoming the “dominant population” for functional cure. In turn, the functional cure will further promote the recovery of HBV specific immune function, which is also the theoretical basis for complete cure of hepatitis B. In the future, the complete cure of chronic HBV infection must be the combination of three drugs: inhibiting virus replication, reducing surface antigen levels and specific immune regulation, among which specific immunotherapy is indispensable. Here we review the relationship, mechanism and clinical significance between the cure of hepatitis B and immune system.

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Remodeling of B-Cell Subsets in Blood during Pegylated IFNα-2a Therapy in Patients with Chronic Hepatitis B Infection

Cited by 9 publications

References 38 publications

B Cell-mediated Humoral Immunity in Chronic Hepatitis B Infection

B Cell-mediated Humoral Immunity in Chronic Hepatitis B Infection

Immunomodulation Induced During Interferon-α Therapy Impairs the Anti-HBV Immune Response Through CD24+CD38hi B Cells

Hepatitis B functional cure and immune response

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