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CD19+CD24hiCD38hi regulatory B cells: a potential immune predictive marker of severity and therapeutic responsiveness of hepatitis C.

ABSTRACT: OBJECTIVES:Hepatitis C virus (HCV) infection is associated with abnormal immune responses. Since regulatory T (Tregs) and B (Bregs) cells modulate the progression of infectious diseases, this study aimed at examining how these cells are involved with the development of HCV infection. METHODS:The frequencies of circulating Bregs and Tregs were characterized using flow cytometry. Both the association and dynamic changes of these cells with related clinical parameters were analyzed after Direct-Acting Antiviral (DAA) agent treatments. Additionally, both regulatory B and T and naïve B and T cells were sorted and stimulated with healthy or HCV sera in vitro. RESULTS:Bregs frequency in HCV-infected patients increased significantly and were positively correlated with levels of sera HCV RNA load, Alanine aminotransferase (AST) and total bilirubin (TBILI). Additionally, the increased Bregs returned to normal levels after DAA treatment. However, Tregs increased markedly in patients with HCV-cirrhosis and were significantly associated with Aspartate aminotransferase to Platelet Ratio Index (APRI) and Fibrosis 4 (FIB-4) scores. Furthermore, HCV sera doesn't expand either Tregs or Bregs, however, it does induce the IL-10 expression in B cells although it fails to induce FOXP3 expression in CD4+ T cells. CONCLUSIONS:Increased Bregs not only may be associated with poor viral eradication and liver injury but also may provide a predictive marker of HCV disease therapeutic efficacy following DAA-treatment. HCV sera may selectively induce Bregs. Tregs probably do not control disease status in the early stages but may contribute to the progression of liver fibrosis in the late stages of HCV infection.

SUBMITTER: Fang Q

PROVIDER: S-EPMC7137049 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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CD19<sup>+</sup>CD24<sup>hi</sup>CD38<sup>hi</sup> regulatory B cells: a potential immune predictive marker of severity and therapeutic responsiveness of hepatitis C.

Fang Qiannan Q Deng Yanan Y Liang Rongzhen R Mei Yongyu Y Hu Zhaoxia Z Wang Julie J Sun Jianbo J Zhang Xiaohong X Bellanti Joseph A JA Zheng Song Guo SG

American journal of translational research 20200315 3

<h4>Objectives</h4>Hepatitis C virus (HCV) infection is associated with abnormal immune responses. Since regulatory T (Tregs) and B (Bregs) cells modulate the progression of infectious diseases, this study aimed at examining how these cells are involved with the development of HCV infection.<h4>Methods</h4>The frequencies of circulating Bregs and Tregs were characterized using flow cytometry. Both the association and dynamic changes of these cells with related clinical parameters were analyzed a ...[more]

PMID: 32269721

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Project description:AimTo investigate interferon-γ-inducible protein-10's (IP-10) potential to anticipate rapid (RVR)- and sustained virological responses (SVR) to chronic hepatitis C (CHC) treatment.MethodsWe included case series examining RVR or SVR in relation to 24 or 48 wk treatment for CHC, in patients treatment free for at least six months, with genotype 1 or 4, and in relation to 24 wk treatment for genotype 2 and 3, with pegylated interferon in combination with ribavirin. Patients had to have both a baseline IP-10 level as well as a hepatitis C virus (HCV)-RNA determination 4 wk after treatment initiation or 24 wk after end of treatment. Studies including patients with liver diseases other than CHC, human immunodeficiency virus-infection, treatment with immunosuppresents or cytostatica, alcohol dependency or active intravenous drug-use were excluded. We found 81 articles by searching the MEDLINE and EMBASE databases. Eight studies were eligible for inclusion. Their quality were assesed using an 18 point checklist for case series, developed using a modified Delphi technique. Information was extracted from the articles, and no raw data was requisitioned. The review protocol was registered at the International Prospective Register of Systematic Reviews (reg. number: CRD42014008736).ResultsThree studies reported on baseline IP-10 level in association with RVR. A signigficant association was found for HCV genotype 1 infection by two studies. Only two studies reported on HCV genotype 4 infected and genotype 2 and 3 infected patients, respectively. A trend was seen for an association between RVR and baseline IP-10 for genotype 4, while no association was found for genotype 2 and 3. Seven studies provided information regarding baseline IP-10 and SVR. Following the pattern regarding rapid virological response all five studies examining SVR in relation to baseline IP-10 levels for HCV, genotype 1 infected patients showed a significant association. Likewise a significant association was seen for HCV, genotype 4 infected, while no association was found for HCV, genotype 2 and 3 infected. Though only two studies examined the assosiation for HCV genotype 4 infected and HCV genotype 2 and 3 infected respectively.ConclusionWe found indications of a possible association between baseline IP-10 level and virological responses in patients with CHC genotype 1 and 4.

Dataset Information

CD19+CD24hiCD38hi regulatory B cells: a potential immune predictive marker of severity and therapeutic responsiveness of hepatitis C.

Publications

CD19<sup>+</sup>CD24<sup>hi</sup>CD38<sup>hi</sup> regulatory B cells: a potential immune predictive marker of severity and therapeutic responsiveness of hepatitis C.

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