Ambikan Anoop T, Cederholm Axel, Rezene Sefanit, Aranda-Guillén Maribel, Nordqvist Hampus, Treutiger Carl Johan, Lira-Junior Ronaldo, Landegren Nils, Gupta Soham
The Systems Virology Laboratory, Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, 141 52, Stockholm, Sweden.
Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala university, Uppsala, Sweden.
Sci Rep. 2025 Sep 1;15(1):32149. doi: 10.1038/s41598-025-17054-6.
Severe COVID-19 is characterized by immune-coagulation dysregulation, yet the contribution of related autoantibodies remains poorly understood. We investigated relationships between plasma autoantibody reactivities, whole-blood transcriptomics, plasma proteomics, and clinical laboratory parameters in a cohort of hospitalized COVID-19 patients. Transcriptomic analysis revealed that 42 curated coagulation and complement cascade genes were upregulated in severe cases compared to healthy controls, with 15 genes, including CR1L, ELANE, ITGA2B, ITGB3, VWF, TFPI, PROS1, MMRN1, and SELP (> 1.2 log2 fold-change), also significantly different from mild cases. Autoantibody profiling against eight coagulation-related proteins (ADAMTS13, Factor V, Protein S, SERPINC1, Apo-H, PROC1, Prothrombin, and PF4) showed reactivities below positivity thresholds across all groups. Using an exploratory approach, in severe cases, subthreshold autoantibody candidates (FDR < 0.25) showed negative correlation trends with select gene expressions and inflammatory markers (Factor V with IL-6 and CXCL10), suggesting potential disease-specific immunomodulatory associations. In contrast, while mild cases exhibited stronger gene-protein correlations, they showed limited associations with antigen reactivities or clinical laboratory parameters. Additionally, no correlations were observed between autoantibodies and platelet-counts or Fibrin-D-dimer levels. Age-associated increases in antigen reactivities were noted in severe disease, implying a role for immunosenescence. These findings support further investigation into the role of subthreshold autoantibody candidates in thromboinflammatory COVID-19 pathogenesis.
重症新型冠状病毒肺炎（COVID-19）的特征是免疫凝血失调，但相关自身抗体的作用仍知之甚少。我们在一组住院的COVID-19患者中研究了血浆自身抗体反应性、全血转录组学、血浆蛋白质组学和临床实验室参数之间的关系。转录组分析显示，与健康对照相比，42个经过整理的凝血和补体级联基因在重症病例中上调，其中15个基因，包括CR1L、ELANE、ITGA2B、ITGB3、VWF、TFPI、PROS1、MMRN1和SELP（>1.2 log2倍变化），也与轻症病例有显著差异。针对八种凝血相关蛋白（ADAMTS13、因子V、蛋白S、SERPINC1、载脂蛋白H、PROC1、凝血酶原和PF4）的自身抗体谱分析显示，所有组的反应性均低于阳性阈值。采用探索性方法，在重症病例中，亚阈值自身抗体候选物（FDR<0.25）与特定基因表达和炎症标志物（因子V与IL-6和CXCL10）呈负相关趋势，提示潜在的疾病特异性免疫调节关联。相比之下，轻症病例虽然表现出更强的基因-蛋白质相关性，但它们与抗原反应性或临床实验室参数的关联有限。此外，未观察到自身抗体与血小板计数或纤维蛋白D-二聚体水平之间的相关性。在重症疾病中，观察到抗原反应性随年龄增加，这意味着免疫衰老起了作用。这些发现支持进一步研究亚阈值自身抗体候选物在血栓性炎症性COVID-19发病机制中的作用。
