Characterization of immune response after cardiac surgery with cardiopulmonary bypass in young infants

Abstract

Introduction

Cardiac surgeries with cardiopulmonary bypass (CPB) cause a complex systemic immuno-inflammatory response, which can lead to postoperative morbidity, particularly in young children. A better understanding of mechanisms involved is needed to improve the outcome. In a whole blood transcriptome study, we have recently identified 2,175 differentially expressed genes after CPB, mainly associated with the immune response. A group of 24 co-expressed immune-related genes correlated with postoperative complications was also identified.

Objective

To validate the transcriptomic analysis data by flow cytometry.

Methods

Peripheral blood mononuclear cells (PBMC) have been isolated from whole blood (4 ml EDTA tube) before and immediately after CPB in children less than 3 months of age after obtaining parental consent. The extensive phenotype of myeloid and lymphoid cells and their ability to secrete cytokines after in vitro stimulation were assessed using flow cytometry. Surface expression of proteins encoded by 5 of 24 co-expressed immune-related genes (VSIG4, LILRB4, LTF, MSR1 and PGLYRP1) were also investigated.

Results/Expected results

Among 6 patients included (Table 1), we noted important phenotypic changes of immune cells after CPB. The expression of HLA-DR, CD11b, CD86 in CD14 + cells (monocytes) and CD3 + lymphocytes function (PD1, ICOS) are decreased on their surfaces after CPB (Fig. 1). After lipopolysaccharide (LPS) in vitro stimulation, monocytes display an altered ability to produce IL1β after CPB (Median Fluorescence Intensity MFI : 2620 1610 - 3975 vs 3786 3200 - 7538, p = 0.03). Finally, as suggested by transcriptomic analysis, monocytic expression of some immune-related proteins (MSR1 and VSIG4) is modified by CPB.

Conclusion/Perspectives

We reported an immediate immune dysfunction after CPB, concerning myeloid and lymphoid cells. The involvement of MSR1 and VSIG4 genes, previously unknown in the CPB-related inflammation, need to be further explored to improve post-operative outcome.