Institute of Neuropathology, University of Zurich, 8091 Zurich, Switzerland; Division of Medical Immunology, Department of Laboratory Medicine, University Hospital Basel, 4031 Basel, Switzerland.
Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
Clin Immunol. 2023 Dec;257:109845. doi: 10.1016/j.clim.2023.109845. Epub 2023 Nov 22.
COVID-19-associated coagulopathy, shown to increase the risk for the occurrence of thromboses and microthromboses, displays phenotypic features of the antiphospholipid syndrome (APS), a prototype antibody-mediated autoimmune disease. Several groups have reported elevated levels of criteria and non-criteria antiphospholipid antibodies (aPL), assumed to cause APS, during acute or post-acute COVID-19. However, disease heterogeneity of COVID-19 is accompanied by heterogeneity in molecular signatures, including aberrant cytokine profiles and an increased occurrence of autoantibodies. Moreover, little is known about the association between autoantibodies and the clinical events. Here, we first aim to characterise the antiphospholipid antibody, anti-SARS-CoV-2 antibody, and the cytokine profiles in a diverse collective of COVID-19 patients (disease severity: asymptomatic to intensive care), using vaccinated individuals and influenza patients as comparisons. We then aim to assess whether the presence of aPL in COVID-19 is associated with an increased incidence of thrombotic events in COVID-19.
We conducted anti-SARS-CoV-2 IgG and IgA microELISA and IgG, IgA, and IgM antiphospholipid line immunoassay (LIA) against 10 criteria and non-criteria antigens in 155 plasma samples of 124 individuals, and we measured 16 cytokines and chemokines in 112 plasma samples. We additionally employed clinical and demographic parameters to conduct multivariable regression analyses within multiple paradigms. In line with recent results, we find that IgM autoantibodies against annexin V (AnV), β2-glycoprotein I (β2GPI), and prothrombin (PT) are enriched upon infection with SARS-CoV-2. There was no evidence for seroconversion from IgM to IgG or IgA. PT, β2GPI, and AnV IgM as well as cardiolipin (CL) IgG antiphospholipid levels were significantly elevated in the COVID-19 but not in the influenza or control groups. They were associated predominantly with the strength of the anti-SARS-CoV-2 antibody titres and the major correlate for thromboses was SARS-CoV-2 disease severity.
While we have recapitulated previous findings, we conclude that the presence of the aPL, most notably PT, β2GPI, AnV IgM, and CL IgG in COVID-19 are not associated with a higher incidence of thrombotic events.
与 COVID-19 相关的凝血功能障碍会增加血栓和微血栓形成的风险，其表现出抗磷脂综合征（APS）的表型特征，APS 是一种典型的抗体介导的自身免疫性疾病。有几个研究小组报告称，在急性或急性后 COVID-19 期间，与 COVID-19 相关的凝血功能障碍会导致 APS 相关的标准和非标准抗磷脂抗体（aPL）水平升高。然而，COVID-19 的疾病异质性伴随着分子特征的异质性，包括异常的细胞因子谱和自身抗体的发生率增加。此外，人们对自身抗体与临床事件之间的关系知之甚少。在这里，我们首先使用接种个体和流感患者作为对照，在不同的 COVID-19 患者（疾病严重程度：无症状至重症监护）中，使用接种个体和流感患者作为对照，来描述 COVID-19 患者的抗磷脂抗体、抗 SARS-CoV-2 抗体和细胞因子谱。然后，我们旨在评估 COVID-19 中 aPL 的存在是否与 COVID-19 中血栓形成事件的发生率增加有关。
我们对 124 名个体的 155 份血浆样本进行了抗 SARS-CoV-2 IgG 和 IgA 微量 ELISA 和 IgG、IgA 和 IgM 抗磷脂线免疫分析（LIA），针对 10 项标准和非标准抗原进行了检测，并对 112 份血浆样本中的 16 种细胞因子和趋化因子进行了检测。我们还使用临床和人口统计学参数在多个范式中进行了多变量回归分析。与最近的结果一致，我们发现针对 annexin V (AnV)、β2-glycoprotein I (β2GPI) 和凝血酶原 (PT) 的 IgM 自身抗体在感染 SARS-CoV-2 后会增加。没有证据表明 IgM 向 IgG 或 IgA 的血清转换。COVID-19 组中 PT、β2GPI 和 AnV IgM 以及心磷脂（CL）IgG 抗磷脂水平显著升高，而流感组和对照组则没有。它们主要与抗 SARS-CoV-2 抗体滴度的强度相关，而血栓形成的主要相关性是 SARS-CoV-2 疾病严重程度。
虽然我们已经重复了以前的发现，但我们的结论是，COVID-19 中 aPL 的存在，特别是 PT、β2GPI、AnV IgM 和 CL IgG，与血栓形成事件发生率的增加无关。
