Abstract

 COVID-19 manifests with a wide spectrum of clinical phenotypes that 

 are characterized by exaggerated and misdirected host immune

 responses1–6. While pathological innate immune activation is well

 documented in severe disease1, the impact of autoantibodies on

 disease progression is less defined. Here, we used a high-

 throughput autoantibody (AAb) discovery technique called Rapid

 Extracellular Antigen Profiling (REAP)7 to screen a cohort of 194 SARS-

 CoV-2 infected COVID-19 patients and healthcare workers for

 autoantibodies against 2,770 extracellular and secreted proteins (the

 “exoproteome”). We found that COVID-19 patients exhibit dramatic

 increases in autoantibody reactivities compared to uninfected 

 controls, with a high prevalence of autoantibodies against

 immunomodulatory proteins including cytokines, chemokines,

 complement components, and cell surface proteins. We established 

 that these autoantibodies perturb immune function and impair

 virological control by inhibiting immunoreceptor signaling and by

 altering peripheral immune cell composition, and found that murine

 surrogates of these autoantibodies exacerbate disease severity in a

 mouse model of SARS-CoV-2 infection. Analysis of autoantibodies

 against tissue-associated antigens revealed associations with 

 specific clinical characteristics and disease severity. In summary, 

 these findings implicate a pathological role for exoproteome-directed

 autoantibodies in COVID-19 with diverse impacts on immune

 functionality and associations with clinical outcomes.

Corresponding authors

Correspondence to Akiko Iwasaki or Aaron M. Ring.

https://www.nature.com/articles/

s41586-021-03631-y

近日，耶鲁大学医学院Akiko Iwasaki和Aaron M. Ring作为共同通讯作者，在Nature发表了题为：Diverse Functional Autoantibodies in Patients with COVID-19的研究论文。该研究发现新冠病毒感染患者体内会出现大量针对自身的抗体，扰乱机体免疫功能，加重病情。

　首先研究团队使用REAP7的通量自身抗体发现方法，筛选了194名SARS-CoV-2感染的COVID-19患者和医疗保健工作者，以获得抗2770种细胞外和分泌蛋白（即“外蛋白组”）的自身抗体。研究发现与未受感染的对照组相比，COVID-19患者的自身抗体反应性显著增加，抗免疫调节蛋白（包括细胞因子、趋化因子、补体成分和细胞表面蛋白）的自身抗体的高患病率。

　　(Fig1.COVID-19患者的免疫靶向性自身抗体具有功能作用)

　　该研究院队并确定这些自身抗体通过抑制免疫受体信号传导和改变外周免疫细胞组成干扰免疫功能和损害病毒学控制，并发现这些自身抗体的小鼠替代物在SARS-CoV-2感染的小鼠模型中加重疾病严重性。对组织相关抗原自身抗体的分析显示与特定的临床特征和疾病严重程度相关。
该研究构建了新冠病毒感染患者体内自身抗体图谱，也找到了能极大影响免疫反应和临床预后的特定自身抗体。

　　(Fig2.免疫靶向性自身抗体加重COVID-19小鼠模型的疾病严重性)

https://www.163.com/dy/article/

GAKFFG020511VCHN.html

 Nature：新冠病毒感染后，

   我们自身的抗体是如何助纣为虐的

文/生物世界 2021-05-23 21:28:08 来源：中国网医疗频道

该研究构建了新冠病毒感染患者体内自身抗体图谱，

也找到了能极大影响免疫反应和临床预后的特定自身抗体。

http://med.china.com.cn/content/

pid/263997/tid/1026