Leite Giuseppe G F, Sousa Mônica Bragança, Rodrigues Larissa de Oliveira C P, Brunialti Milena Karina Colo, Medina-Pestana José, Butler Joe M, Peters-Sengers Hessel, Requião-Moura Lúcio, Salomão Reinaldo
Division of Infectious Diseases, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Division of Nephrology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Front Immunol. 2024 Dec 16;15:1508110. doi: 10.3389/fimmu.2024.1508110. eCollection 2024.
The COVID-19 pandemic has significantly impacted global health, especially in vulnerable populations like kidney transplant recipients (KTRs). Recently, mass spectrometry-based proteomics has emerged as a powerful tool to shed light on a broad spectrum of dysregulated biological processes in KTRs with COVID-19. In this study, we prospectively collected blood samples from 17 COVID-19-positive KTRs and 10 non-infected KTRs between May and September 2020. Using tandem mass tag-based quantitative proteomics, we analyzed peripheral blood mononuclear cells (PBMCs), plasma protein biomarkers, and lymphocyte counts, followed by bioinformatics analysis. Our results revealed significant proteomic alterations in COVID-19-infected KTRs, particularly in pathways related to glycolysis, glucose metabolism, and neutrophil degranulation. Additionally, we observed an altered immune response characterized by elevated cytokines and decreased lymphocyte counts. Notably, KTRs with AKI exhibited worse clinical outcomes, including higher rates of ICU admission and mechanical ventilation. Comparative analysis of PBMC proteomic profiles between AKI and non-AKI patients identified distinct immune-related pathways, with AKI patients showing marked changes in innate immune responses, particularly neutrophil degranulation. Furthermore, we observed a negative correlation between T cell counts and neutrophil degranulation, suggesting a role for immune dysregulation in COVID-19. Our findings provide critical insights into the immune and metabolic responses in COVID-19-infected KTRs, especially those with AKI, highlighting the need for focused research and therapeutic strategies targeting immune dysregulation in this high-risk population.
2019冠状病毒病（COVID-19）大流行对全球健康产生了重大影响，尤其是在肾移植受者（KTRs）等弱势群体中。最近，基于质谱的蛋白质组学已成为一种强大的工具，有助于揭示感染COVID-19的KTRs中广泛失调的生物学过程。在本研究中，我们于2020年5月至9月前瞻性收集了17例COVID-19阳性KTRs和10例未感染KTRs的血样。使用基于串联质量标签的定量蛋白质组学，我们分析了外周血单核细胞（PBMCs）、血浆蛋白生物标志物和淋巴细胞计数，随后进行了生物信息学分析。我们的结果显示，感染COVID-19的KTRs存在显著的蛋白质组学改变，特别是在与糖酵解、葡萄糖代谢和中性粒细胞脱颗粒相关的途径中。此外，我们观察到免疫反应发生改变，其特征是细胞因子升高和淋巴细胞计数减少。值得注意的是，患有急性肾损伤（AKI）的KTRs临床结局更差，包括更高的重症监护病房（ICU）入住率和机械通气率。对AKI和非AKI患者的PBMC蛋白质组学谱进行比较分析，确定了不同的免疫相关途径，AKI患者在先天免疫反应中表现出明显变化，尤其是中性粒细胞脱颗粒。此外，我们观察到T细胞计数与中性粒细胞脱颗粒之间存在负相关，这表明免疫失调在COVID-19中起作用。我们的研究结果为感染COVID-19的KTRs，尤其是患有AKI的患者的免疫和代谢反应提供了关键见解，强调了针对这一高危人群免疫失调进行重点研究和治疗策略的必要性。
