The analysis of neutrophil-activating autoantibodies: a thrombosis perspective

• Grant number: 23/13356-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: December 24, 2023
• End date: September 28, 2024
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Otávio Cabral Marques
• Grantee: Dennyson Leandro Mathias da Fonseca
• Supervisor: Guido Moll
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Charité - Universitätsmedizin Berlin, Germany
• Associated to the scholarship: 20/16246-2 - Holistic characterization of T cell exhaustion in patients with Zika, BP.DD

Abstract

We recently showed that older patients with severe COVID-19 have high levels of autoantibodies (aab) against molecules targeting Cardiolipin and Platelet glycoprotein compared to healthy controls. In this case, we found that, in particular, anti-cardiolipin1 and anti-platelet antibodies increase the risk of thrombosis-related events such as pulmonary thromboembolism and deep vein thrombosi, which we have recently characterized in COVID-19 patients. this regard, autoimmune diseases and aab may differ physiologically. There has been extensive discussion regarding the physiology of aab as participants in various homeostatic processes. This project aims to understand the relation of neutrophil-activating aab in the modulation of NET release and neutrophil oxidative burst. Thus, to gain insights into the biological pathways dysregulated in neutrophils from thrombus, which could be dysregulated by anti-neutrophils activating aab, we will analyze bulk and scRNAseq data from chronic thrombus as well as the autoantibodyome of these patients. The dysregulated neutrophil-activating aab will be functionally validated using mechanistic approaches, such as by the analysis of neutrophil respiratory burst, phagocytic activity, and neutrophils extracellular traps (NET) release and microbicidal activity in the presence or absence of aab. Therefore, this project will provide a comprehensive overview of neutrophil-activating aab participation in physiological processes, opening new avenues to understand aab physiology and thrombosis development in COVID-19 and other infectious diseases.