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.
Highlights
The detection of autoantibodies directed against phosphatidylethanolamine has been proposed to improve the diagnosis and management of patients presenting clinical manifestations of antiphospholipid syndrome (APS), such as thrombosis and/or obstetric diseases, and who are persistently negative for conventional markers including lupus coagulant (LA), IgG and/or IgM anticardiolipin autoantibodies and IgG and/or IgM anti β2 glycoprotein I autoantibodies
Since human B2-glycoprotein I (B2GPI) was coated with PE in the commercial ELISA, adsorption experiments were conducted on immobilized B2GPI to further explore discrepancies between the two ELISA systems (Figure 2)
Wtheesehxowpleodr,afotirotnheofifrsAt PtimS,eeinspecially patients with unexplained thrombosis, that oxidative stress was higher in against phosphatidylethanolamine (aPE)-positive than in aPE-negative patients, raising an interesting hypothesis on the mechanism of action of aPE in thrombosis
Summary
The detection of autoantibodies directed against phosphatidylethanolamine (aPE) has been proposed to improve the diagnosis and management of patients presenting clinical manifestations of antiphospholipid syndrome (APS), such as thrombosis and/or obstetric diseases, and who are persistently negative for conventional markers including lupus coagulant (LA), IgG and/or IgM anticardiolipin autoantibodies (aCL) and IgG and/or IgM anti β2 glycoprotein I autoantibodies (aβ2GPI). Numerous antiphospholipid autoantibodies (aPL) target anionic phospholipid, aPEs are directed against a zwitterionic neutral phospholipid made up of a glycerol molecule esterified by two fatty acids and a phosphoethanolamine residue. Several studies highlighted the positivity of aPEs in thrombotic events, even in the absence of conventional antiphospholipid autoantibodies (aPL), reinforcing their potential interest as diagnostic markers. Since endosomes are of key importance for protein intracellular trafficking, it is suggested that aPEs could have a broad impact on different types of cells. These autoantibodies could especially contribute to the dysregulation of membrane redox enzymes and stimulate reactive oxygen species (ROS)-mediated signaling pathways. TBARs measure the global effects of ROS production, and more importantly the effects of tissue damage, and its level is influenced by the ratio of oxidizing/pro-oxidizing agents [16]
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