Schaenman Joanna M, Rossetti Maura, Korin Yael, Sidwell Tiffany, Groysberg Victoria, Liang Emily, Vangala Sitaram, Wisniewski Nicholas, 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. 2018 Apr;79(4):203-212. doi: 10.1016/j.humimm.2018.01.011. Epub 2018 Feb 1.
Immunologic impairment may contribute to poor outcomes after implantation of mechanical circulatory support device (MCSD), with infection often as a terminal event. The study of immune dysfunction is of special relevance given the growing numbers of older patients with heart disease. The aim of the study was to define which immunologic characteristics are associated with development of adverse clinical outcomes after MCSD implantation. We isolated peripheral blood mononuclear cells (PBMC) from patients pre- and up to 20 days post-MCSD implantation and analyzed them by multiparameter flow cytometry for T cell dysfunction, including terminal differentiation, exhaustion, and senescence. We used MELD-XI and SOFA scores measured at each time point as surrogate markers of clinical outcome. Older patients demonstrated increased frequencies of terminally differentiated T cells as well as NKT cells. Increased frequency of terminally differentiated and immune senescent T cells were associated with worse clinical outcome as measured by MELD-XI and SOFA scores, and with progression to infection and death. In conclusion, our data suggest that T cell dysfunction, independently from age, is associated with poor outcomes after MCSD implantation, providing a potential immunologic mechanism behind patient vulnerability to multiorgan dysfunction and death. This noninvasive approach to PBMC evaluation holds promise for candidate evaluation and patient monitoring.
免疫功能受损可能导致机械循环支持装置(MCSD)植入后预后不良,感染常为终末事件。鉴于患心脏病老年患者数量不断增加,免疫功能障碍的研究具有特殊意义。本研究的目的是确定哪些免疫特征与MCSD植入后不良临床结局的发生相关。我们从MCSD植入前及植入后长达20天的患者中分离外周血单个核细胞(PBMC),并用多参数流式细胞术分析其T细胞功能障碍,包括终末分化、耗竭和衰老。我们将每个时间点测量的MELD-XI和SOFA评分用作临床结局的替代指标。老年患者终末分化T细胞以及NKT细胞的频率增加。终末分化和免疫衰老T细胞频率增加与MELD-XI和SOFA评分所衡量的更差临床结局相关,也与感染进展和死亡相关。总之,我们的数据表明,T细胞功能障碍独立于年龄,与MCSD植入后不良结局相关,为患者易发生多器官功能障碍和死亡提供了潜在的免疫机制。这种评估PBMC的非侵入性方法在候选评估和患者监测方面具有前景。