Is Oxidative Stress an Emerging Player in the Thrombosis of Patients with Anti-Phosphatidylethanolamine Autoantibodies?

authors

• Heim Xavier
• Bertin Daniel
• Resseguier Noémie
• Metral Audrey
• Beziane Abdelouahab
• Brodovitch Alexandre
• Guieu Régis
• Steinberg Jean-Guillaume
• Blot-Chabaud Marcel
• Morange Pierre-Emmanuel
• Mege Jean-Louis
• Bardin Nathalie

keywords

• Reactive oxygen species ROS
• Thrombosis
• Anti-phosphatidylethanolamine autoantibodies
• ELISA
• Antiphospholipid syndrome
• Thiobarbituric acid-reactive substances TBARs

abstract

The detection of anti-phosphatidylethanolamine autoantibodies (aPEs) has been proposed to improve the diagnosis and management of patients presenting clinical manifestations of antiphospholipid syndrome (APS), such as thrombosis, and who are persistently negative for conventional markers. After selecting the most specific ELISA for their detection, we evidenced the interest of aPEs in the exploration of thrombosis when APS conventional markers were negative through a 1-year retrospective study including 1131 consecutive patients routinely tested for aPEs. To validate this result, we assessed aPEs in a newly selected population of 77 patients with unexplained deep vein thrombosis (DVT). With a total prevalence of 19.5%, we confirmed the interest of aPE detection in patients with unexplained DVT who were devoid of other aPLs markers. Since endosomal compartment, a source of ROS production, has been recently identified as the cellular target of aPEs in vitro, we then investigated an association between aPE positivity and reactive oxygen species (ROS) production by measuring the production of thiobarbituric acid-reactive substances. We showed, for the first time, a significant association between aPE positivity and systemic ROS production in patients which led us to hypothesize a new mechanism of action of aPEs in thrombosis through a signaling related to oxidative stress.

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