Serological analysis reveals an imbalanced IgG subclass composition associated with COVID-19 disease severity.
Serological analysis reveals an imbalanced IgG subclass composition associated with COVID-19 disease severity.
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DOI：
10.1016/j.xcrm.2021.100329
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发表时间：
2021-07-20
期刊：
影响因子：
--
通讯作者：
Lee WT
中科院分区：
文献类型：
--
作者：
Yates JL;Ehrbar DJ;Hunt DT;Girardin RC;Dupuis AP 2nd;Payne AF;Sowizral M;Varney S;Kulas KE;Demarest VL;Howard KM;Carson K;Hales M;Ejemel M;Li Q;Wang Y;Peredo-Wende R;Ramani A;Singh G;Strle K;Mantis NJ;McDonough KA;Lee WT
2019冠状病毒病（COVID-19）与广泛的疾病表现相关，从无症状感染到急性呼吸窘迫综合征（ARDS）。矛盾的是，有人认为COVID-19疾病严重程度与循环中的严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）特异性抗体水平（包括病毒中和滴度）之间存在直接关系。对536名康复期医护人员的血清学分析显示，在经历严重疾病的个体中，sars - cov -2特异性抗体和病毒中和抗体水平升高。sars - cov -2特异性抗体的严重相关升高主要由免疫球蛋白G （IgG）主导，IgG亚类比例偏向于受体结合域(RBD)-和s1特异性IgG3的升高。此外，患有严重疾病的个体显示出与炎症受体Fc RIIIa结合的sars - cov -2特异性抗体升高。基于这些相关研究，我们提出刺特异性IgG亚类的利用可能通过fc介导的有效效应功能影响COVID-19疾病严重程度。这些结果可能对SARS-CoV-2疫苗设计和恢复期血浆治疗具有重要意义。SARS-CoV-2抗体水平和中和效价随COVID-19严重程度上升IgG1和IgG3主导着SARS-CoV-2恢复期抗体池，与严重COVID-19相关的峰值特异性IgG3亚类比率增加，在严重COVID-19队列中观察到增强的Fc - RIIIa结合。他们的分析显示，IgG亚类比例倾向于IgG3，与COVID-19疾病严重程度相关。作者假设IgG3、Fc效应物功能与严重COVID-19的炎症特征之间存在联系。
Coronavirus disease 2019 (COVID-19) is associated with a wide spectrum of disease presentation, ranging from asymptomatic infection to acute respiratory distress syndrome (ARDS). Paradoxically, a direct relationship has been suggested between COVID-19 disease severity and the levels of circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies, including virus-neutralizing titers. A serological analysis of 536 convalescent healthcare workers reveals that SARS-CoV-2-specific and virus-neutralizing antibody levels are elevated in individuals that experience severe disease. The severity-associated increase in SARS-CoV-2-specific antibody is dominated by immunoglobulin G (IgG), with an IgG subclass ratio skewed toward elevated receptor binding domain (RBD)- and S1-specific IgG3. In addition, individuals that experience severe disease show elevated SARS-CoV-2-specific antibody binding to the inflammatory receptor FcɣRIIIa. Based on these correlational studies, we propose that spike-specific IgG subclass utilization may contribute to COVID-19 disease severity through potent Fc-mediated effector functions. These results may have significant implications for SARS-CoV-2 vaccine design and convalescent plasma therapy. Levels of SARS-CoV-2 antibodies and neutralizing titers rise with COVID-19 severity IgG1 and IgG3 dominate the SARS-CoV-2 convalescent antibody pool Increases in spike-specific IgG3 subclass ratios correlate with severe COVID-19 Enhanced FcɣRIIIa binding is observed in severe COVID-19 cohorts In a serological analysis of convalescent healthcare workers, Yates et al. explore antibody profiles associated with COVID-19 severity. Their analysis reveals an IgG subclass ratio skewed toward IgG3 that correlates with COVID-19 disease severity. The authors hypothesize a link between IgG3, Fc effector functions, and inflammation characteristic of severe COVID-19.
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