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 E, Puri Rajan, Renz Harald, Schapiro Jeffrey, Weidenbacher Payton A, Wittman Richard, Ahuja Neera, Chung Ho-Ryun, Jagannathan Prasanna, James Judith A, Kim Peter S, Meyer Nuala J, Nadeau Kari C, Radic Marko, Robinson William H, Singh Upinder, Wang Taia T, Wherry E John, Skevaki Chrysanthi, Luning Prak Eline T, Utz Paul J
Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
Nat Commun. 2021 Sep 14;12(1):5417. doi: 10.1038/s41467-021-25509-3.
COVID-19 is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. Here we develop three protein arrays to measure IgG autoantibodies associated with connective tissue diseases, anti-cytokine antibodies, and anti-viral antibody responses in serum from 147 hospitalized COVID-19 patients. Autoantibodies are identified in approximately 50% of patients but in less than 15% of healthy controls. When present, autoantibodies largely target autoantigens associated with rare disorders such as myositis, systemic sclerosis and overlap syndromes. A subset of autoantibodies targeting traditional autoantigens or cytokines develop de novo following SARS-CoV-2 infection. Autoantibodies track with longitudinal development of IgG antibodies recognizing SARS-CoV-2 structural proteins and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. 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.
新型冠状病毒肺炎(COVID-19)与多种临床表现相关,包括自身免疫特征和自身抗体产生。在此,我们开发了三种蛋白质阵列,以检测147例住院COVID-19患者血清中与结缔组织疾病相关的IgG自身抗体、抗细胞因子抗体和抗病毒抗体反应。约50%的患者检测到自身抗体,而健康对照中这一比例不到15%。当自身抗体存在时,其主要靶向与罕见疾病如肌炎、系统性硬化症和重叠综合征相关的自身抗原。一部分靶向传统自身抗原或细胞因子的自身抗体在感染严重急性呼吸综合征冠状病毒2(SARS-CoV-2)后新发产生。自身抗体与识别SARS-CoV-2结构蛋白和一部分非结构蛋白的IgG抗体的纵向发展相关,但与流感、季节性冠状病毒或其他致病病毒的蛋白无关。我们得出结论,SARS-CoV-2在相当比例的住院COVID-19患者中导致新发IgG自身抗体的产生,且与针对SARS-CoV-2蛋白的免疫反应呈正相关。