靶向血管紧张素 II 受体 1（AGTR1）的失调自身抗体与 COVID-19 症状的积累有关。
Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms.
作者信息
Fonseca Dennyson Leandro M, Jäpel Maj, Gyamfi Michael Adu, Filgueiras Igor Salerno, Baiochi Gabriela Crispim, Ostrinski Yuri, Halpert Gilad, Lavi Yael Bublil, Vojdani Elroy, Silva-Sousa Thayna, Usuda Júlia Nakanishi, E Silva Juan Carlo Santos, Freire Paula P, Nóbile Adriel Leal, Adri Anny Silva, Barcelos Pedro Marçal, Corrêa Yohan Lucas Gonçalves, do Vale Fernando Yuri Nery, Lopes Letícia Oliveira, Schmidt Solveig Lea, Wang Xiaoqing, Vahldieck Carl, Fels Benedikt, Schimke Lena F, Cabral-Miranda Gustavo, Hirata Mario Hiroyuki, AKhan Taj Ali, Yu Yen-Rei A, Dalmolin Rodrigo Js, Amital Howard, Vojdani Aristo, Dias Haroldo Dutra, Nakaya Helder, Ochs Hans D, Silverberg Jonathan I, Zimmerman Jason, Zyskind Israel, Rosenberg Avi Z, Schulze-Forster Kai, Heidecke Harald, Catar Rusan, Moll Guido, Hackel Alexander, Kusche-Vihrog Kristina, Shoenfeld Yehuda, Riemekasten Gabriela, Akbarzadeh Reza, Marques Alexandre H C, Cabral-Marques Otavio
机构信息
BIH Center for Regenerative Therapies (BCRT), Julius Wolff Institute (JWI), and Berlin Institute of Health (BIH); all Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), 10117, Berlin, Germany.
Interunit Postgraduate Program on Bioinformatics, Institute of Mathematics and Statistics (IME), University of Sao Paulo (USP), Sao Paulo, SP, Brazil.
出版信息
NPJ Syst Biol Appl. 2025 Jan 13;11(1):7. doi: 10.1038/s41540-025-00488-z.
Coronavirus disease 2019 (COVID-19) presents a wide spectrum of symptoms, the causes of which remain poorly understood. This study explored the associations between autoantibodies (AABs), particularly those targeting G protein-coupled receptors (GPCRs) and renin‒angiotensin system (RAS) molecules, and the clinical manifestations of COVID-19. Using a cross-sectional analysis of 244 individuals, we applied multivariate analysis of variance, principal component analysis, and multinomial regression to examine the relationships between AAB levels and key symptoms. Significant correlations were identified between specific AABs and symptoms such as fever, muscle aches, anosmia, and dysgeusia. Notably, anti-AGTR1 antibodies, which contribute to endothelial glycocalyx (eGC) degradation, a process reversed by losartan, have emerged as strong predictors of core symptoms. AAB levels increased with symptom accumulation, peaking in patients exhibiting all four key symptoms. These findings highlight the role of AABs, particularly anti-AGTR1 antibodies, in determining symptom severity and suggest their involvement in the pathophysiology of COVID-19, including vascular complications.
2019冠状病毒病（COVID-19）呈现出广泛的症状，其病因仍知之甚少。本研究探讨了自身抗体（AABs），特别是那些靶向G蛋白偶联受体（GPCRs）和肾素-血管紧张素系统（RAS）分子的自身抗体与COVID-19临床表现之间的关联。通过对244名个体的横断面分析，我们应用多变量方差分析、主成分分析和多项回归来检验AAB水平与关键症状之间的关系。在特定的AABs与发热、肌肉疼痛、嗅觉丧失和味觉障碍等症状之间发现了显著相关性。值得注意的是，抗AGTR1抗体可导致内皮糖萼（eGC）降解，而氯沙坦可逆转这一过程，该抗体已成为核心症状的强预测指标。AAB水平随着症状的累积而升高，在出现所有四种关键症状的患者中达到峰值。这些发现突出了AABs，特别是抗AGTR1抗体在确定症状严重程度方面的作用，并表明它们参与了COVID-19的病理生理过程，包括血管并发症。
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