Schaenman Joanna M, Rossetti Maura, Sidwell Tiffany, Groysberg Victoria, Sunga Gemalene, Liang Emily, Vangala Sitaram, Chang Eleanor, Bakir Maral, Bondar Galyna, Cadeiras Martin, Kwon Murray, Reed Elaine F, Deng Mario
Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, Los Angeles, CA 90095, United States.
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, Los Angeles, CA 90095, United States.
Hum Immunol. 2019 Feb;80(2):126-134. doi: 10.1016/j.humimm.2018.11.004. Epub 2018 Nov 14.
Noninvasive immunologic analysis of peripheral blood holds promise for explaining the mechanism of development of adverse clinical outcomes, and may also become a method for patient risk stratification before or after mechanical circulatory support device (MCSD) implantation. Dysregulation of the innate immune system is associated with increased patient age but has yet to be evaluated in the older patient with advanced heart failure undergoing MCSD surgery. Patients pre- and post-MCSD implantation had peripheral blood mononuclear cells (PBMC) and serum isolated. Multiparameter flow cytometry was used to analyze markers of innate cell function, including monocyte subtypes. Multiplex cytokine analysis was performed. MELD-XI and SOFA scores were utilized as surrogate markers of outcomes. Increased levels of pro-inflammatory cytokines including IL-15, TNF-α, and IL-10 were associated with increased MELD-XI and SOFA scores. IL-8, TNF- α, and IL-10 were associated with risk of death after MCSD implantation, even with correction for patient age. Increased frequency of 'classical' monocytes (CD14 + CD16-) were associated with increased MELD-XI and SOFA scores. This suggests that inflammation and innate immune system activation contribute to progression to multiorgan system failure and death after MCSD surgery. Development of noninvasive monitoring of peripheral blood holds promise for biomarker development for candidate selection and patient risk stratification.
外周血的非侵入性免疫分析有望解释不良临床结局的发生机制,也可能成为机械循环支持装置(MCSD)植入前后患者风险分层的一种方法。固有免疫系统失调与患者年龄增加有关,但在接受MCSD手术的老年晚期心力衰竭患者中尚未得到评估。对MCSD植入前后的患者分离外周血单个核细胞(PBMC)和血清。采用多参数流式细胞术分析固有细胞功能标志物,包括单核细胞亚型。进行多重细胞因子分析。MELD-XI和SOFA评分用作结局的替代标志物。包括IL-15、TNF-α和IL-10在内的促炎细胞因子水平升高与MELD-XI和SOFA评分增加相关。即使校正患者年龄,IL-8、TNF-α和IL-10也与MCSD植入后的死亡风险相关。“经典”单核细胞(CD14 + CD16-)频率增加与MELD-XI和SOFA评分增加相关。这表明炎症和固有免疫系统激活有助于MCSD手术后进展为多器官系统衰竭和死亡。外周血非侵入性监测的发展有望为候选者选择和患者风险分层开发生物标志物。