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，耶魯大學醫學院Akiko Iwasaki和Aaron M. Ring作為共同通訊作者，在Nature發表了題為：Diverse Functional Autoantibodies in Patients with COVID-19的研究論文。該研究發現新冠病毒感染患者體內會出現大量針對自身的抗體，擾亂機體免疫功能，加重病情。

　首先研究團隊使用REAP7的通量自身抗體發現方法，篩選了194名SARS-CoV-2感染的COVID-19患者和醫療保健工作者，以獲得抗2770種細胞外和分泌蛋白（即“外蛋白組”）的自身抗體。研究發現與未受感染的對照組相比，COVID-19患者的自身抗體反應性顯著增加，抗免疫調節蛋白（包括細胞因子、趨化因子、補體成分和細胞表面蛋白）的自身抗體的高患病率。

　　(Fig1.COVID-19患者的免疫靶向性自身抗體具有功能作用)

　　該研究院隊並確定這些自身抗體通過抑制免疫受體信號傳導和改變外周免疫細胞組成干擾免疫功能和損害病毒學控制，並發現這些自身抗體的小鼠替代物在SARS-CoV-2感染的小鼠模型中加重疾病嚴重性。對組織相關抗原自身抗體的分析顯示與特定的臨床特徵和疾病嚴重程度相關。
該研究構建了新冠病毒感染患者體內自身抗體圖譜，也找到了能極大影響免疫反應和臨床預後的特定自身抗體。

　　(Fig2.免疫靶向性自身抗體加重COVID-19小鼠模型的疾病嚴重性)

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

GAKFFG020511VCHN.html

 Nature：新冠病毒感染後，

   我們自身的抗體是如何助紂為虐的

文/生物世界 2021-05-23 21:28:08 來源：中國網醫療頻道

該研究構建了新冠病毒感染患者體內自身抗體圖譜，

也找到了能極大影響免疫反應和臨床預後的特定自身抗體。

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

pid/263997/tid/1026