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Increased eryptosis in patients with primary antiphospholipid syndrome (APS): a new actor in the pathogenesis of APS


1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14

 

  1. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  2. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  3. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  4. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  5. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  6. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  7. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  8. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  9. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  10. Department of Translational and Precision Medicine, Haematology, Sapienza University of Rome, Italy.
  11. Department of Translational and Precision Medicine, Haematology, Sapienza University of Rome, Italy.
  12. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  13. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy.
  14. Department of Clinical Internal, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Italy. cristiano.alessandri@uniroma1.it

CER13567
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PMID: 33124577 [PubMed]

Received: 14/05/2020
Accepted : 06/07/2020
In Press: 29/10/2020

Abstract

OBJECTIVES:
Antiphospholipid syndrome (APS) is an autoimmune disease characterised by a hypercoagulable state and the presence of antiphospholipid antibodies (aPL). During the mechanism of red blood cells (RBCs) death, called eryptosis, RBCs can adhere to vascular wall participating in the development of a pro-thrombotic state. It is known that enhanced eryptosis contributes to several pathological conditions but the role of this process in APS has not been investigated yet. We analysed spontaneous eryptosis in a cohort of APS patients and aPL carriers (asymptomatic subjects with positive aPL tests). The effect on eryptosis of antibodies (Abs) purified from serum of APS patients and aPL carriers was also investigated.
METHODS:
In this study, 30 patients with primary APS (PAPS) and 17 aPL carriers were recruited. Twenty healthy donors (HD) and 13 patients affected by autoimmune haemolytic anaemia (AHIA) were also recruited. RBCs were incubated with PAPS and aPL carriers Abs, purified by ammonium sulfate precipitation. Levels of eryptosis were analysed by flow cytometry.
RESULTS:
In vitro Abs from APS patients induced eryptosis in RBCs isolated from HD after 4 h of culture. On the contrary, Abs from aPL carriers had no effect on the percentage of phosphatidylserine-exposing RBCs. Ex vivo, APS patients showed higher levels of spontaneous eryptosis compared to HD and aPL carriers.
CONCLUSIONS:
In this study, we demonstrated a potential new aspect of APS pathogenesis based on the ability of Abs isolated from APS patients, not identified in aPL carriers, to stimulate eryptosis suggesting a possible contribution of this process in the clinical manifestations of APS.

Rheumatology Article