Department of Internal Medicine 1, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Deutsches Zentrum Immuntherapie (DZI), 91054 Erlangen, Germany.
Cells. 2020 Dec 12;9(12):2676. doi: 10.3390/cells9122676.
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to an adaptive immune response in the host and the formation of anti-SARS-CoV-2 specific antibodies. While IgG responses against SARS-CoV-2 have been characterized quite well, less is known about IgA. IgA2 activates immune cells and induces inflammation and neutrophil extracellular trap (NET) formation which may contribute to organ injury and fatal outcome in SARS-CoV-2-infected patients. SARS-CoV-2 spike protein specific antibody levels were measured in plasma samples of 15 noninfected controls and 82 SARS-CoV-2-infected patients with no or mild symptoms, moderate symptoms (hospitalization) or severe disease (intensive care unit, ICU). Antibody levels were compared to levels of C-reactive protein (CRP) and circulating extracellular DNA (ecDNA) as markers for general inflammation and NET formation, respectively. While levels of SARS-CoV-2-specific IgG were similar in all patient groups, IgA2 antibodies were restricted to severe disease and showed the strongest discrimination between nonfatal and fatal outcome in patients with severe SARS-CoV-2 infection. While anti-SARS-CoV-2 IgG and IgA2 levels correlated with CRP levels in severely diseased patients, only anti-SARS-CoV-2 IgA2 correlated with ecDNA. These data suggest that the formation of anti-SARS-CoV-2 IgA2 during SARS-CoV-2 infection is a marker for more severe disease related to NET formation and poor outcome.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染会导致宿主产生适应性免疫反应，并形成针对 SARS-CoV-2 的特异性抗体。虽然针对 SARS-CoV-2 的 IgG 反应已经得到了很好的描述，但对 IgA 的了解较少。IgA2 可激活免疫细胞，诱导炎症和中性粒细胞胞外陷阱（NET）形成，这可能导致 SARS-CoV-2 感染患者的器官损伤和致命结局。在 15 名未感染对照者和 82 名无或轻度症状、中度症状（住院）或严重疾病（重症监护病房，ICU）的 SARS-CoV-2 感染患者的血浆样本中测量了针对 SARS-CoV-2 刺突蛋白的特异性抗体水平。将抗体水平与 C 反应蛋白（CRP）和循环细胞外 DNA（ecDNA）水平进行了比较，分别作为一般炎症和 NET 形成的标志物。虽然所有患者组的 SARS-CoV-2 特异性 IgG 水平相似，但 IgA2 抗体仅限于严重疾病，并在严重 SARS-CoV-2 感染患者的非致死性和致死性结局之间表现出最强的区分能力。虽然 SARS-CoV-2 特异性 IgG 和 IgA2 水平与重病患者的 CRP 水平相关，但只有 SARS-CoV-2 特异性 IgA2 与 ecDNA 相关。这些数据表明，在 SARS-CoV-2 感染期间形成针对 SARS-CoV-2 的 IgA2 是与 NET 形成和不良结局相关的更严重疾病的标志物。
