Cofactor-independent human antiphospholipid antibodies induce venous thrombosis in mice

Journal of Thrombosis and Haemostasis : JTH
D ManukyanKarl J Lackner

Abstract

Essentials Cofactor-independent antiphospholipid antibodies (CI-aPL) are generally considered non-pathogenic. We analyzed the effects of human monoclonal CI-aPL in a mouse model of venous thrombosis. As shown in vitro, CI-aPL induce a procoagulant state in vivo by activation of endosomal NADPH-oxidase. Contrary to common belief, CI-aPL induce venous thrombosis in vivo. Background There is general consensus that the antiphospholipid syndrome (APS) is caused by antiphospholipid antibodies (aPL) with antibodies against β2-glycoprotein-I being the most relevant. aPL that bind phospholipids in the absence of protein cofactors are generally considered pathogenetically irrelevant. We showed that cofactor-independent human monoclonal aPL isolated from APS patients induce proinflammatory and procoagulant cellular responses by activating endosomal NADPH-oxidase 2 (NOX2). Similar aPL were detected in all IgG fractions from APS patients analyzed. Objectives We aimed to clarify if cofactor-independent aPL can be thrombogenic in vivo and, if so, whether these effects are mediated via activation of NOX2. Methods Two cofactor-independent human monoclonal aPL, HL5B and RR7F, were tested in a mouse model of venous thrombosis. Genetically modifie...Continue Reading

References

Oct 1, 1992·American Journal of Reproductive Immunology : AJRI·Y Shoenfeld
Oct 1, 1996·Lupus·S S Pierangeli, E N Harris
Jun 13, 1998·The Journal of Clinical Investigation·H Weiler-GuettlerR D Rosenberg
Jan 7, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ingrid MüllerBernd Engelmann
Jan 8, 2003·The Journal of Experimental Medicine·Steffen MassbergBernhard Nieswandt
May 5, 2005·Journal of Thrombosis and Haemostasis : JTH·D KirchhoferS Bunting
Aug 30, 2005·Annals of the New York Academy of Sciences·Catharina BuschmannPhilipp von Landenberg
Oct 4, 2006·Immunobiology·Christian FischerPhilipp von Landenberg
Aug 3, 2010·Nature Medicine·Steffen MassbergBernd Engelmann
May 11, 2011·Nature Reviews. Rheumatology·Pier Luigi MeroniFrancesco Tedesco
Nov 8, 2011·Seminars in Arthritis and Rheumatism·Katie PoultonIan Giles
Mar 28, 2012·The Journal of Experimental Medicine·Marie-Luise von BrühlSteffen Massberg
Apr 19, 2012·Seminars in Thrombosis and Hemostasis·Rohan WillisSilvia S Pierangeli
May 4, 2012·Blood·Philip G de Groot, Rolf T Urbanus
May 29, 2012·Lupus·P G de GrootR H W M Derksen
Mar 15, 2013·The New England Journal of Medicine·Bill Giannakopoulos, Steven A Krilis
Mar 13, 2014·Journal of Thrombosis and Haemostasis : JTH·K J BrandtP de Moerloose

❮ Previous
Next ❯

Citations

Feb 18, 2016·Journal of Thrombosis and Haemostasis : JTH·N Mackman, R A S Roubey
Mar 22, 2016·Journal of Thrombosis and Haemostasis : JTH·K J Lackner, N Müller-Calleja
Apr 1, 2017·Current Rheumatology Reports·Karl J LacknerNadine Müller-Calleja
Mar 25, 2017·British Journal of Haematology·Deepa R J Arachchillage, Mike Laffan
May 26, 2017·Current Opinion in Rheumatology·Andrew P VreedeJason S Knight
Dec 3, 2016·Annals of the Rheumatic Diseases·Nadine Müller-CallejaKarl J Lackner
Jul 15, 2018·Journal of Thrombosis and Haemostasis : JTH·K J Lackner, N Müller-Calleja
Feb 14, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Steven P Grover, Nigel Mackman
Nov 10, 2018·Expert Review of Clinical Immunology·Karl J Lackner, Nadine Müller-Calleja
Jan 13, 2018·Nature Reviews. Disease Primers·Karen SchreiberBeverley J Hunt
Dec 4, 2019·Expert Review of Clinical Immunology·May ChoiLeslie Skeith
Oct 16, 2019·Journal of Thrombosis and Thrombolysis·Anne HollerbachKarl J Lackner
Oct 21, 2016·Journal of Thrombosis and Haemostasis : JTH·K J Lackner, N Müller-Calleja
Oct 28, 2016·Hämostaseologie·Karl J LacknerNadine Müller-Calleja
Jun 2, 2016·Antibodies·Karl J Lackner, Nadine Müller-Calleja
Mar 15, 2020·International Journal of Molecular Sciences·Clemens GutmannAlberto Smith
Mar 13, 2021·Science·Nadine Müller-CallejaWolfram Ruf
Mar 17, 2021·Autoimmunity Reviews·Yannick DieudonnéVincent Gies
Apr 4, 2021·International Journal of Molecular Sciences·Alex A GandhiJason S Knight
Jul 10, 2021·Journal of Thrombosis and Haemostasis : JTH·Anne HollerbachKarl J Lackner
Dec 12, 2017·Best Practice & Research. Clinical Rheumatology·Philip G de Groot, Bas de Laat

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Polyendocrinopathies

Autoimmune polyendocrinopathies, also called polyglandular autoimmune syndromes (PGASs), or polyendocrine autoimmune syndromes(PASs), are a heterogeneous group of rare diseases characterized by autoimmune activity against more than one endocrine organ, although non-endocrine organs can be affected. Discover the latest research on autoimmune polyendocrinopathies here.

Autoimmune Polyendocrine Syndromes

This feed focuses on a rare genetic condition called Autoimmune Polyendocrine Syndromes, which are characterized by autoantibodies against multiple endocrine organs. This can lead to Type I Diabetes.

Antiphospholipid Syndrome

Antiphospholipid syndrome or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by the presence of antibodies directed against phospholipids.

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.