Autoantibodies against ACE2 and angiotensin type-1 receptors increase severity of COVID-19

被引:61
作者
Rodriguez-Perez, Ana, I [1 ,2 ]
Labandeira, Carmen M. [1 ,3 ]
Pedrosa, Maria A. [1 ,2 ]
Valenzuela, Rita [1 ,2 ]
Suarez-Quintanilla, Juan A. [4 ]
Cortes-Ayaso, Maria [5 ]
Mayan-Conesa, Placido [5 ]
Labandeira-Garcia, Jose L. [1 ,2 ]
机构
[1] Univ Santiago de Compostela, Res Ctr Mol Med & Chron Dis CIMUS, IDIS, Santiago De Compostela, Spain
[2] Networking Res Ctr Neurodegenerat Dis CIBERNED, Madrid, Spain
[3] Hosp Alvaro Cunqueiro, Univ Hosp Complex, Vigo, Spain
[4] Univ Santiago de Compostela, Primary Hlth Care Unit Fontinas, IDIS, Santiago De Compostela, Spain
[5] Univ Clin Hosp Santiago, Emergency Dept, Santiago De Compostela, Spain
关键词
Autoantibody; Autoimmunity; LIGHT; Outcome prediction; Renin-angiotensin system; SARS-CoV-2; AGONISTIC AUTOANTIBODIES; TNF SUPERFAMILY; I RECEPTOR; PREECLAMPSIA; LIGHT; ALPHA; SARS; HYPERTENSION; PATHOGENESIS; CONTRIBUTES;
D O I
10.1016/j.jaut.2021.102683
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The renin-angiotensin system (RAS) plays a major role in COVID-19. Severity of several inflammation-related diseases has been associated with autoantibodies against RAS, particularly agonistic autoantibodies for angiotensin type-1 receptors (AA-AT1) and autoantibodies against ACE2 (AA-ACE2). Disease severity of COVID-19 patients was defined as mild, moderate or severe following the WHO Clinical Progression Scale and determined at medical discharge. Serum AA-AT1 and AA-ACE2 were measured in COVID-19 patients (n = 119) and non-infected controls (n = 23) using specific solid-phase, sandwich enzyme-linked immunosorbent assays. Serum LIGHT (TNFSF14; tumor necrosis factor ligand superfamily member 14) levels were measured with the corresponding assay kit. At diagnosis, AA-AT1 and AA-ACE2 levels were significantly higher in the COVID-19 group relative to controls, and we observed significant association between disease outcome and serum AA-AT1 and AA-ACE2 levels. Mild disease patients had significantly lower levels of AA-AT1 (p < 0.01) and AA-ACE2 (p < 0.001) than moderate and severe patients. No significant differences were detected between males and females. The increase in autoantibodies was not related to comorbidities potentially affecting COVID-19 severity. There was significant positive correlation between serum levels of AA-AT1 and LIGHT (TNFSF14; rPearson = 0.70, p < 0.001). Both AA-AT1 (by agonistic stimulation of AT1 receptors) and AA-ACE2 (by reducing conversion of Angiotensin II into Angiotensin 1-7) may lead to increase in AT1 receptor activity, enhance proinflammatory responses and severity of COVID-19 outcome. Patients with high levels of autoantibodies require more cautious control after diagnosis. Additionally, the results encourage further studies on the possible protective treatment with AT1 receptor blockers in COVID-19.
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页数:8
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