Abstract Body (Do not enter title and authors here): Background
Congenital heart diseases (CHD) are the most common birth defects. Previous studies have revealed the susceptibility of CHD patients to immunodeficiency; however, the heterogeneity of immune cells landscape underlying CHD patients remains poorly understood.
Research question
Are peripheral blood mononuclear cells dysregulated in pediatric CHD patients?
Aims
We aimed to investigate the landscape of peripheral blood mononuclear cells in CHD patients with conotruncal defects by comparison against healthy controls.
Methods
Peripheral blood samples were collected in 5 patients with conotruncal defects and 3 healthy children. We conducted single-cell transcriptome analysis on peripheral blood mononuclear cells from these samples.
Results
The scheme of whole study was shown in Figure 1A. A total of 44,530 cells were identified after quality-control, clustered into 8 groups, and annotated with canonical PBMC markers (Figure 1B). Compared with healthy controls, patients were characterized with a prominent decrease in natural killer T (NKT) cells and an increased proportion of monocytes were observed (Figure 1C). Zooming into NK-like cells confirmed a significant contribution of NKT cells in difference between groups, whilst other types were similar in both groups (Figure 2A). The differentially expressed gene in NKT were enriched in pathway involving T helper cells differentiation, signal transduction and regulation (Figure 2B). Furthermore, NKT in patients showed a significantly lower proliferation score in contrast with a higher apoptosis score (Figure 2C & D). Although monocytes in patients were more in quantity, the composition of CD14⁺ and CD16⁺ subtypes were comparable between groups (Figure 3A). Concordantly, apoptosis score of monocytes were similar. However, the T cell proliferation score was lower in case group (Figure 3B & C). In addition, CD14⁺ and CD16⁺ monocytes both showed distinct transcriptome between groups and the differentially expressed genes were prevalently enriched in inflammation-related pathways (Figure 3D & E).
Conclusion
Single-cell analysis revealed a dysregulated PBMC landscape in pediatric patients with conotruncal defects, exhibiting a prominent decrease in NKT population and an increased proportion of monocytes. Transcriptome analysis further indicated a less mature immune phenotype in NKT and monocytes differentiation. Future study is warranted to further investigate the roles of these cells on immunoregulation in these patients.