TIMELESS is a key gene mediating thrombogenesis in COVID-19 and antiphospholipid syndrome

• Published in: Scientific reports 2022-10, Vol.12 (1), p.17248-17248, Article 17248
• Main Authors: Zhang, Wenjing, Di, Longjiang, Liu, Zhongshuang, sun, Qi, Wu, Yan, Wang, Nuan, Jin, Meili, Gao, Lingling, Zhang, Mengyu
• Format: Article
• Language: English
• Subjects: 631/114; 631/250; Antibodies, Antiphospholipid; Antiphospholipid antibodies; Antiphospholipid syndrome; Antiphospholipid Syndrome - complications; Antiphospholipid Syndrome - genetics; Autoantibodies; Autoimmune diseases; Autophagy; Bioinformatics; Circadian rhythms; Coronaviruses; COVID-19; COVID-19 - genetics; Critical Illness; Genes; Genomes; Humanities and Social Sciences; Humans; Immunotherapy; Leukocytes (mononuclear); multidisciplinary; Phospholipids; Science; Science (multidisciplinary); Thromboembolism; Thrombosis; Thrombosis - etiology; Transcriptomes
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-21694-3

Abnormal coagulation and increased risk of thrombosis are some of the symptoms associated with COVID-19 severity. Anti-phospholipid antibodies (aPLs) present in critically ill COVID-19 patients contribute to systemic thrombosis. The aim of this study was to identify key common genes to characterize genetic crosstalk between COVID-19 and antiphospholipid syndrome (APS) using bioinformatics analysis and explore novel mechanisms of immune-mediated thrombosis in critically ill COVID-19 patients. The transcriptome data of mononuclear cells from severe COVID-19 patients and APS patients were evaluated to obtain the common genes. The protein–protein interaction network and cytoHubba module analysis in Cytoscape software were used to find the associated hinge genes and hub genes. Among the common differentially expressed genes, TIMELESS depletion was identified only in patients with severe COVID-19 and not in patients with mild COVID-19, and it was validated with the GSE159678 dataset. Functional analyses using gene ontology terms and the Kyoto Encyclopedia of Genes and Genomes pathway suggested that TIMELESS might contribute to the production of antiphospholipid antibody and thrombosis in both COVID-19 and APS patients. The potential role of TIMELESS and autophagy genes in momonuclear cells were further investigated, and GSK3B was found to be associated with TIMELESS. Autophagy targeting agents have a therapeutic potential against COVID-19 and thrombogenesis in APS, which may be related to the role of autophagy genes in the modification of circadian clock proteins. Interference with TIMELESS and other genes associated with it to regulate autoantibody expression may be a potential strategy for immunotherapy against thrombogenesis in severe COVID-19 patients.