PgRNA closely correlates to cytokine profile in HBeAg-positive pregnant women undergoing prophylactic antiviral intervention

Front Immunol. 2024 Dec 11:15:1511855. doi: 10.3389/fimmu.2024.1511855. eCollection 2024.

Abstract

Background: Previous studies primarily focused on the effects of ALT and virology, but there is a lack of research on the correlations of HBcrAg and pgRNA, two novel virologic markers, with immunological parameters in pregnant women with CHB undergoing prophylactic antiviral intervention.

Methods: We conducted a retrospective cohort study involving 28 HBeAg-positive pregnant women with CHB undergoing prophylactic antiviral intervention. Clinical data, virological markers (HBV DNA, HBsAg, HBeAg, HBcrAg and pgRNA) and 28 cytokines were detected at three time points: 24-28 weeks gestation (before prophylactic antiviral intervention), near birth and within 3 months postpartum.

Results: PgRNA was moderately (correlation coefficient between 0.4 and 0.6) positively correlated with Th1-type cytokines (IFN-γ, IL12p70, IL2, and TNF-α), Th17-type cytokines (IL21), Th2-type cytokines (IL10, IL4, and IL5), and cytokines regulating cell proliferation and differentiation (CTLA4, IL15, IL23, and TGF-β1) and moderately negatively correlated with EGF (correlation coefficient = -0.4), while ALT, HBV-DNA, HBsAg and HBcrAg were insignificantly correlated with cytokines at 24-28 weeks of gestation. Most cytokines tended to be elevated, with statistically significant increases observed only for the chemokines IP10 and MCP-1 during pregnancy. Most cytokines were significantly increased in postpartum women with virologic rebound after treatment discontinuation postpartum, but no significant change in the Th1/Th2 ratio. Changes in virologic markers were significantly correlated with cytokines. Immune activation was more pronounced in postpartum women who developed ALT flare compared to who did not, with Th1-type cytokines (especially IL12p40) and chemokines being main differential cytokines.

Conclusion: PgRNA was more closely correlated with cytokine profiles, and postpartum ALT flare may be the result of the interaction between Th1-type cytokines and chemokines.

Keywords: ALT flare; HBcrAg; PgRNA; chronic hepatitis B; cytokine; hepatitis B virus; immune; pregnancy.

MeSH terms

  • Adult
  • Antiviral Agents* / therapeutic use
  • Biomarkers / blood
  • Cytokines* / blood
  • DNA, Viral / blood
  • Female
  • Hepatitis B e Antigens* / blood
  • Hepatitis B e Antigens* / immunology
  • Hepatitis B virus* / immunology
  • Hepatitis B, Chronic* / blood
  • Hepatitis B, Chronic* / drug therapy
  • Hepatitis B, Chronic* / immunology
  • Hepatitis B, Chronic* / virology
  • Humans
  • Pregnancy
  • Pregnancy Complications, Infectious / blood
  • Pregnancy Complications, Infectious / immunology
  • Pregnancy Complications, Infectious / virology
  • Retrospective Studies
  • Young Adult

Substances

  • Cytokines
  • Hepatitis B e Antigens
  • Antiviral Agents
  • Biomarkers
  • DNA, Viral

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was funded in part by grants from the Chongqing Talents Project (cstc2021ycjh-bgzxm0150), the First batch of key Disciplines on Public Health in Chongqing, Health Commission of Chongqing, China, the Remarkable Innovation–Clinical Research Project, The Second Affiliated Hospital of Chongqing Medical University and Scientific and the Technological Research Program of Chongqing Municipal Education Commission, The Second Affiliated Hospital of Chongqing Medical University (KJZD-K202300404).