Chang Sarah Esther, Feng Allan, Meng Wenzhao, Apostolidis Sokratis A, Mack Elisabeth, Artandi Maja, Barman Linda, Bennett Kate, Chakraborty Saborni, Chang Iris, Cheung Peggie, Chinthrajah Sharon, Dhingra Shaurya, Do Evan, Finck Amanda, Gaano Andrew, Geßner Reinhard, Giannini Heather M, Gonzalez Joyce, Greib Sarah, Gündisch Margrit, Hsu Alex Ren, Kuo Alex, Manohar Monali, Mao Rong, Neeli Indira, Neubauer Andreas, Oniyide Oluwatosin, Powell Abigail Elizabeth, Puri Rajan, Renz Harald, Schapiro Jeffrey M, Weidenbacher Payton A, Wittman Rich, Ahuja Neera, Chung Ho-Ryun, Jagannathan Pras, James Judith, Kim Peter S, Meyer Nuala J, Nadeau Kari, Radic Marko, Robinson William H, Singh Upinder, Wang Taia T, Wherry E John, Skevaki Chrysanthi, Prak Eline T Luning, Utz P J
medRxiv. 2021 Jan 29:2021.01.27.21250559. doi: 10.1101/2021.01.27.21250559.
Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. We developed three different protein arrays to measure hallmark IgG autoantibodies associated with Connective Tissue Diseases (CTDs), Anti-Cytokine Antibodies (ACA), and anti-viral antibody responses in 147 hospitalized COVID-19 patients in three different centers. Autoantibodies were identified in approximately 50% of patients, but in <15% of healthy controls. When present, autoantibodies largely targeted autoantigens associated with rare disorders such as myositis, systemic sclerosis and CTD overlap syndromes. Anti-nuclear antibodies (ANA) were observed in ∼25% of patients. Patients with autoantibodies tended to demonstrate one or a few specificities whereas ACA were even more prevalent, and patients often had antibodies to multiple cytokines. Rare patients were identified with IgG antibodies against angiotensin converting enzyme-2 (ACE-2). A subset of autoantibodies and ACA developed following SARS-CoV-2 infection while others were transient. Autoantibodies tracked with longitudinal development of IgG antibodies that recognized SARS-CoV-2 structural proteins such as S1, S2, M, N and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. COVID-19 patients with one or more autoantibodies tended to have higher levels of antibodies against SARS-CoV-2 Nonstructural Protein 1 (NSP1) and Methyltransferase (ME). We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and are positively correlated with immune responses to SARS-CoV-2 proteins.
2019冠状病毒病（COVID-19）由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起，与多种临床表现相关，包括自身免疫特征和自身抗体产生。我们开发了三种不同的蛋白质阵列，以测量147名在三个不同中心住院的COVID-19患者中与结缔组织病（CTD）相关的标志性IgG自身抗体、抗细胞因子抗体（ACA）和抗病毒抗体反应。在约50%的患者中检测到自身抗体，但在<15%的健康对照中检测到。当自身抗体存在时，它们主要靶向与罕见疾病如肌炎、系统性硬化症和CTD重叠综合征相关的自身抗原。在约25%的患者中观察到抗核抗体（ANA）。有自身抗体的患者倾向于表现出一种或几种特异性，而ACA更为普遍，患者通常有针对多种细胞因子的抗体。少数患者被鉴定出具有抗血管紧张素转换酶2（ACE-2）的IgG抗体。一部分自身抗体和ACA在SARS-CoV-2感染后出现，而其他的则是短暂的。自身抗体与识别SARS-CoV-2结构蛋白（如S1、S2、M、N）和一部分非结构蛋白但不识别流感、季节性冠状病毒或其他致病病毒蛋白的IgG抗体的纵向发展相关。有一种或多种自身抗体的COVID-19患者往往具有更高水平的针对SARS-CoV-2非结构蛋白1（NSP1）和甲基转移酶（ME）的抗体。我们得出结论，SARS-CoV-2在相当一部分住院COVID-19患者中导致新发IgG自身抗体的产生，并且与对SARS-CoV-2蛋白的免疫反应呈正相关。
