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

E. André, C. Bridonneau, C. Jacqueline, M. Davieau, V. Gourain, A. Roquilly, A. Chenouard
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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.

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婴幼儿体外循环心脏手术后免疫反应的特点
体外循环心脏手术(CPB)引起复杂的全身免疫炎症反应,这可能导致术后发病率,特别是在幼儿中。为了改善结果,需要更好地了解所涉及的机制。在一项全血转录组研究中,我们最近发现了2175个CPB后差异表达基因,主要与免疫反应相关。还发现了一组24个与术后并发症相关的共表达免疫相关基因。目的用流式细胞术验证转录组学分析数据。方法经家长同意,从3月龄以下患儿全血(4 ml EDTA管)中分离外周血单个核细胞(PBMC)。骨髓细胞和淋巴细胞在体外刺激后的广泛表型及其分泌细胞因子的能力被流式细胞术评估。我们还研究了24个共表达免疫相关基因(VSIG4、LILRB4、LTF、MSR1和PGLYRP1)中5个基因编码蛋白的表面表达。结果/预期结果在纳入的6例患者中(表1),我们注意到CPB后免疫细胞的重要表型变化。CPB后,CD14 +细胞(单核细胞)和CD3 +淋巴细胞(PD1, ICOS)表面HLA-DR, CD11b, CD86的表达减少(图1)。体外脂多糖(LPS)刺激后,CPB后单核细胞显示出产生il - 1β的能力改变(中位荧光强度MFI: 2620 1610 - 3975 vs 3786 3200 - 7538, p = 0.03)。最后,转录组学分析表明,CPB修饰了一些免疫相关蛋白(MSR1和VSIG4)的单核细胞表达。结论/观点我们报道了CPB后立即出现的免疫功能障碍,涉及骨髓和淋巴细胞。在cpb相关炎症中,先前未知的MSR1和VSIG4基因的参与,需要进一步探索以改善术后预后。
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来源期刊
Archives of Cardiovascular Diseases Supplements
Archives of Cardiovascular Diseases Supplements CARDIAC & CARDIOVASCULAR SYSTEMS-
自引率
0.00%
发文量
508
期刊介绍: Archives of Cardiovascular Diseases Supplements is the official journal of the French Society of Cardiology. The journal publishes original peer-reviewed clinical and research articles, epidemiological studies, new methodological clinical approaches, review articles, editorials, and Images in cardiovascular medicine. The topics covered include coronary artery and valve diseases, interventional and pediatric cardiology, cardiovascular surgery, cardiomyopathy and heart failure, arrhythmias and stimulation, cardiovascular imaging, vascular medicine and hypertension, epidemiology and risk factors, and large multicenter studies. Additionally, Archives of Cardiovascular Diseases also publishes abstracts of papers presented at the annual sessions of the Journées Européennes de la Société Française de Cardiologie and the guidelines edited by the French Society of Cardiology.
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