Amri Nada, Bégin Rémi, Tessier Nolwenn, Vachon Laurent, Villeneuve Louis, Bégin Philippe, Bazin Renée, Loubaki Lionel, Martel Catherine
Faculty of Medicine, Université de Montréal, Pavillon Roger-Gaudry, 2900 Edouard Montpetit Blvd, Montreal, QC H3T 1J4, Canada.
Montreal Heart Institute, 5000 Belanger Street, Montreal, QC H1T 1C8, Canada.
Pharmaceuticals (Basel). 2022 Mar 17;15(3):365. doi: 10.3390/ph15030365.
Convalescent plasma therapy (CPT) has gained significant attention since the onset of the coronavirus disease 2019 (COVID-19) pandemic. However, clinical trials designed to study the efficacy of CPT based on antibody concentrations were inconclusive. Lymphatic transport is at the interplay between the immune response and the resolution of inflammation from peripheral tissues, including the artery wall. As vascular complications are a key pathogenic mechanism in COVID-19, leading to inflammation and multiple organ failure, we believe that sustaining lymphatic vessel function should be considered to define optimal CPT. We herein sought to determine what specific COVID-19 convalescent plasma (CCP) characteristics should be considered to limit inflammation-driven lymphatic endothelial cells (LEC) dysfunction. CCP donated 16 to 100 days after the last day of symptoms was characterized and incubated on inflammation-elicited adult human dermal LEC (aHDLEC). Plasma analysis revealed that late donation correlates with higher concentration of circulating pro-inflammatory cytokines. Conversely, extracellular vesicles (EVs) derived from LEC are more abundant in early donated plasma (r = -0.413, = 0.004). Thus, secretion of LEC-EVs by an impaired endothelium could be an alarm signal that instigate the self-defense of peripheral lymphatic vessels against an excessive inflammation. Indeed, in vitro experiments suggest that CCP obtained rapidly following the onset of symptoms does not damage the aHDLEC junctions as much as late-donated plasma. We identified a particular signature of CCP that would counteract the effects of an excessive inflammation on the lymphatic endothelium. Accordingly, an easy and efficient selection of convalescent plasma based on time of donation would be essential to promote the preservation of the lymphatic and immune system of infected patients.
自2019年冠状病毒病（COVID-19）大流行开始以来，恢复期血浆疗法（CPT）受到了广泛关注。然而，基于抗体浓度研究CPT疗效的临床试验尚无定论。淋巴运输处于免疫反应与包括动脉壁在内的外周组织炎症消退之间的相互作用中。由于血管并发症是COVID-19的关键致病机制，可导致炎症和多器官功能衰竭，我们认为在确定最佳CPT时应考虑维持淋巴管功能。我们在此试图确定应考虑哪些特定的COVID-19恢复期血浆（CCP）特征，以限制炎症驱动的淋巴管内皮细胞（LEC）功能障碍。对症状最后一天后16至100天捐献的CCP进行了表征，并在引发炎症的成人人类真皮LEC（aHDLEC）上进行培养。血浆分析显示，晚期捐献与循环促炎细胞因子浓度较高相关。相反，早期捐献血浆中源自LEC的细胞外囊泡（EVs）更为丰富（r = -0.413，P = 0.004）。因此，受损内皮细胞分泌的LEC-EVs可能是一种警报信号，可促使外周淋巴管对过度炎症进行自我防御。事实上，体外实验表明，症状出现后迅速获得的CCP对aHDLEC连接的损伤不如晚期捐献的血浆严重。我们确定了CCP的一种特定特征，它可以抵消过度炎症对淋巴管内皮的影响。因此，基于捐献时间轻松有效地选择恢复期血浆对于促进感染患者淋巴和免疫系统的保护至关重要。
