Investigating Neutrophil Subpopulations involved in Acute Lung Injury in Pediatric Patients with Congenital Heart Disease using a Single Cell Approach

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B569
Abstract ID: 6314

Presenting Author:
Stefano Gianoli , Postdoctoral Research Fellow at Boston Children's Hosp., Harvard Med. Sch., Harvard Medical School

Abstract:

Congenital Heart Disease (CHD) is a significant health concern (4-10/1,000 live births). Morbidity in CHD includes a younger age, thrombotic complications, and organ dysfunction. Acute lung injury (ALI) occurs intra/postoperatively in 2–3% of pediatric patients, particularly neonates and infants. Neutrophil recruitment to the lungs during CPB-induced ALI is noted. Recognizing the dual role of neutrophils in both defense and tissue damage, a nuanced strategy is essential.

Our preliminary single-cell RNA sequencing (scRNAseq) analysis of blood from pediatric patients undergoing longer (>=3 hours) versus shorter (<3 hours) CPB surgery reveals distinct neutrophil subpopulations to be enriched post-CPB and associated with ALI. Specifically, in patients with a longer CPB, the IFTIM2 gene, associated with type I interferon responses, is enriched. Pathway analysis confirms associations with interferon responses, chemotaxis, cell migration, reactive oxygen species, and cell death. Preliminary data shows that upregulated β2 integrin levels post-longer CPB suggest a predisposition to ALI.

This insight aims to guide the design of targeted therapies for specific neutrophil subpopulations while preserving their critical functions. This study will improve the treatment of these patients, addressing a crucial and critical gap in pediatric cardiac intensive care.