Increased protease-activated receptor 1 autoantibodies are associated with severe COVID-19. Issue 4 (27th December 2022) - Tran, Florian
Immune perturbation is a hallmark of coronavirus disease 2019 (COVID-19), with ambiguous roles of various immune cell compartments. Plasma cells, responsible for antibody production, have a two-pronged response while mounting an immune defence with 1) physiological immune response producing neutralising antibodies against protein structures of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 2) potentially deleterious autoantibody generation. Growing evidence hints towards broad activation of plasma cells and the presence of pathological autoantibodies (abs) that mediate immune perturbation in acute COVID-19 [1]. Recently, a systematic screening for abs confirmed induction of diverse functional abs in SARS-CoV-2 infection, targeting several immunomodulatory proteins, including cytokines/chemokines and their respective G-protein coupled receptors (GPCR) [1]. Abs against GPCR act as agonistic and allosteric receptor modulators and are linked to chronic inflammatory diseases [2] and, as we demonstrated recently, disease severity in acute COVID-19 [3]. In patients with severe #COVID19, increased levels of autoantibodies against PAR1 were found. These might serve as allosteric agonists of PAR1 on endothelial cells and platelets, and thus might contribute to the pathogenesis of microthrombosis in COVID-19. https://bit.ly/3pqM9Vv