Mass Cytometry Reveals Cell Type-specific Immune Remodeling in Placentas of Women with Chronic Hepatitis B Infection.

Abstract

Background and aims: Hepatitis B virus (HBV) vertical transmission remains a major health challenge, and the characteristics of the placental immune microenvironment in chronic infection remain unclear. This study aimed to use mass cytometry to comprehensively analyze phenotypic changes in placental immune cell subsets.

Methods: We collected placental tissues from 20 pregnant women (6 healthy controls and 14 with chronic HBV infection). CD45⁺ leukocytes were detected using a 35-marker antibody panel. Unsupervised clustering identified 14 clusters, of which 13 immune clusters were analyzed.

Results: HBV mainly caused functional remodeling of placental immune cells rather than changes in cell composition (P > 0.05 for all subsets). In natural killer (NK) cells, CD38 (P = 0.015) and CD16 (P = 0.0020) were notably upregulated and strongly correlated (ρ = 0.872, P < 0.001), suggesting potentially enhanced antibody-dependent cellular cytotoxicity (ADCC) function. T cells showed upregulation of CD27, CD38, and CXCR5. Basophils exhibited the most pronounced changes: 9 differential markers (including chemokine receptors CCR4 and CCR7) were consistently downregulated. Classical monocytes showed an M1 polarization tendency (CD38↑, CD163↓). All P-values were raw; no markers remained significant after false discovery rate (FDR) correction at an FDR threshold of < 0.1, indicating nominal significance. In addition, the coordinated expression patterns of markers within multiple cell subsets were weakened after infection.

Conclusions: These exploratory findings suggest that HBV may reshape placental immunity through enhanced NK cell activation, broad basophil suppression, and disrupted marker coordination. The sample size was limited (n = 20), so the results need to be validated in larger cohorts. These findings provide new perspectives for understanding the mechanisms of mother-to-child transmission.