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Merck

Pathogenic lipid-binding antiphospholipid antibodies are associated with severity of COVID-19.

Journal of thrombosis and haemostasis : JTH (2021-07-10)
Anne Hollerbach, Nadine Müller-Calleja, Denise Pedrosa, Antje Canisius, Martin F Sprinzl, Tanja Falter, Heidi Rossmann, Marc Bodenstein, Christian Werner, Ingo Sagoschen, Thomas Münzel, Oliver Schreiner, Visvakanth Sivanathan, Michael Reuter, Johannes Niermann, Peter R Galle, Luc Teyton, Wolfram Ruf, Karl J Lackner
ANOTACE

Coronavirus disease 19 (COVID-19)-associated coagulopathy is a hallmark of disease severity and poor prognosis. The key manifestations of this prothrombotic syndrome-microvascular thrombosis, stroke, and venous and pulmonary clots-are also observed in severe and catastrophic antiphospholipid syndrome. Antiphospholipid antibodies (aPL) are detectable in COVID-19 patients, but their association with the clinical course of COVID-19 remains unproven. To analyze the presence and relevance of lipid-binding aPL in hospitalized COVID-19 patients. Two cohorts of 53 and 121 patients from a single center hospitalized for PCR-proven severe acute respiratory syndrome-coronavirus 2 infection were analyzed for the presence of aPL and clinical severity of COVID-19. We here demonstrate that lipid-binding aPL are common in COVID-19. COVID-19 patients with lipid-binding aPL have higher median concentrations of C-reactive protein and D-dimer, and are more likely to have a critical clinical course and fatal outcome. Lipid-binding aPL isolated from COVID-19 patients target the recently described cell surface complex of lysobisphosphatidic acid (LBPA) with the protein C receptor (EPCR) to induce prothrombotic and inflammatory responses in monocytes and endothelial cells. We show that B1a cells producing lipid-reactive aPL of the IgG isotype circulate in the blood of COVID-19 patients. In vivo, COVID-19 aPL accelerate thrombus formation in an experimental mouse model dependent on the recently delineated signaling pathway involving EPCR-LBPA. COVID-19 patients rapidly expand B1a cells secreting pathogenic lipid-binding aPL with broad thrombotic and inflammatory effects. The association with markers of inflammation and coagulation, clinical severity, and mortality suggests a causal role of aPL in COVID-19-associated coagulopathy.

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Sigma-Aldrich
Cardiolipin solution from bovine heart, 4.7-5.3 mg/mL in ethanol, ≥97% (TLC)