Work

Novel immunologic mechanisms for Fontan-associated liver disease

Year: 2024

Type: article

Abstract: Single ventricle congenital heart disease resulting in Fontan palliation has led to improved survival, however, Fontan-associated liver disease (FALD) is ubiquitous in this population by adulthood. While lymphopenia has been associated with the degree of FALD, potential immunologic mechanisms remain unstudied, and were the focus of this study. Single-nuclei RNA-seq (snRNA-seq) data from liver samples of adolescent Fontan and control patients were analyzed with specific focus on lymphocytes and natural killer (NK) and T-cell fractions. Liver samples from Fontan patients demonstrated upregulation of endothelial cells (ECs: 4.2 ± 1.0 vs. 13.6 ± 3.4 %, p = 0.037) and total lymphocytes (0.7 ± 0.1 vs. 3.6 ± 0.7 %, p = 0.007), more specifically in NK and T-cells (NK: 0.29 ± 0.16 vs. 1.40 ± 0.64 %, p = 0.028 and T-cell: 0.28 ± 0.04 vs. 1.80 ± 1.01 %, p = 0.034). Enhanced genes important in T-cell activation and differentiation were demonstrated, as well as those involved in cell-to-cell adhesion and lymphocyte migration. Supporting lymphocyte trafficking, ECs demonstrated amplification of critical chemotactic and lymphocyte recruitment genes. Increased time from Fontan palliation was associated with more dramatic lymphocytic transcriptomic changes. Hepatic changes in adolescent Fontan patients suggest that T-cells are contributing to the early development and possible progression of FALD. • Fontan patients demonstrate hepatic infiltration of endothelial cells and lymphocytes (natural killer and T-cell populations). • The hepatic transcriptomic profile in Fontan physiology supports endothelial cell facilitation of T-cell recruitment to the liver, and immune-based mechanisms for Fontan-associated liver disease (FALD). • Immunologic changes in FALD appear more advanced with increasing time from Fontan palliation.

Source: International Journal of Cardiology Congenital Heart Disease

DOI: 10.1016/j.ijcchd.2024.100554

Authors: Austin Angelotti, Maninder Dhesi, Shyam S. Bansal, Elisa A. Bradley

Institutions: Pennsylvania State University, Penn State Milton S. Hershey Medical Center

Language: English

Topic: Congenital Heart Disease Studies

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,000