Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Department of Medical Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
Sci Rep. 2024 Oct 18;14(1):24512. doi: 10.1038/s41598-024-75514-x.
While Coronavirus disease 2019 (COVID-19) vaccines have proven to be both effective and generally safe, rare but severe adverse events following immunization (AEFIs) are described. Autoantibodies to platelet factor-4 are associated with catastrophic thrombotic AEFIs, but comprehensive investigations of other autoantibodies are lacking. We aimed to detect and describe autoantibodies targeting coagulation-related proteins in a population-wide cohort (SWEDEGENE) including AEFIs attributed to COVID-19 vaccines in Sweden. Subjects were recruited from December 2020 to October 2022 and were stratified based on diagnosis and COVID-19 exposure. Screening was carried out in two phases, with a multiplex bead-based assay in the first subset (until September 2021) and with targeted assays for the second (until October 2022). Positivity was defined based on absolute, relative, and biological/technical thresholds. Patients with coagulation-related AEFIs were older and the Vaxzevria vaccine was overrepresented in this group. Two cases had antiphospholipid antibodies but none had PF4 antibodies. We identified six positives for protein S autoantibodies. Protein S concentrations were negatively correlated with autoantibody response in patients with immunoreactivity and functional analysis revealed low protein S activity in three subjects. Our population-wide analysis reveals cases with autoantibodies against protein S which possibly underlie coagulopathic AEFIs.
虽然 2019 年冠状病毒病（COVID-19）疫苗已被证明既有效又普遍安全，但仍有罕见但严重的疫苗接种后不良反应（AEFIs）被描述。血小板因子 4 自身抗体与灾难性血栓性 AEFIs 相关，但对其他自身抗体的综合研究还很缺乏。我们旨在检测和描述在瑞典 COVID-19 疫苗相关 AEFIs 的人群（SWEDEGENE）中针对凝血相关蛋白的自身抗体。研究对象于 2020 年 12 月至 2022 年 10 月招募，并根据诊断和 COVID-19 暴露进行分层。筛选分两个阶段进行，第一阶段采用基于多重微珠的检测方法（直至 2021 年 9 月），第二阶段采用靶向检测方法（直至 2022 年 10 月）。阳性结果基于绝对、相对和生物学/技术阈值来定义。与凝血相关的 AEFIs 患者年龄较大，Vaxzevria 疫苗在该组中占比过高。有两例患者有抗磷脂抗体，但均无 PF4 抗体。我们鉴定出 6 例蛋白 S 自身抗体阳性。患者的蛋白 S 浓度与免疫反应性呈负相关，功能分析显示 3 名患者的蛋白 S 活性较低。我们的全人群分析显示了针对蛋白 S 的自身抗体的病例，这些自身抗体可能是导致凝血性 AEFIs 的原因。
