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Thromb Haemost 2002; 87(04): 735-741
DOI: 10.1055/s-0037-1613073
Review Article
Schattauer GmbH

Evidence for Anticoagulant Activity and β2-GPI Accumulation in Late Endosomes of Endothelial Cells Induced by Anti-LBPA Antibodies

M. Sorice
1   Dipartimento di Medicina Sperimentale e Patologia, Università “La Sapienza”, Roma, Italy
,
D. Ferro
2   Clinica Medica I, Università “La Sapienza”, Roma, Italy
,
R. Misasi
1   Dipartimento di Medicina Sperimentale e Patologia, Università “La Sapienza”, Roma, Italy
,
V. Pittoni
3   Cattedra di Reumatologia, Università “La Sapienza”, Roma, Italy
,
A. Longo
1   Dipartimento di Medicina Sperimentale e Patologia, Università “La Sapienza”, Roma, Italy
,
A. Circella
1   Dipartimento di Medicina Sperimentale e Patologia, Università “La Sapienza”, Roma, Italy
,
T. Garofalo
1   Dipartimento di Medicina Sperimentale e Patologia, Università “La Sapienza”, Roma, Italy
,
R. Gradini
1   Dipartimento di Medicina Sperimentale e Patologia, Università “La Sapienza”, Roma, Italy
,
F. Violi
2   Clinica Medica I, Università “La Sapienza”, Roma, Italy
,
J. Gruenberg
4   Biochemistry Department, University of Geneva, Switzerland
,
G. Valesini
1   Dipartimento di Medicina Sperimentale e Patologia, Università “La Sapienza”, Roma, Italy
› Author Affiliations
Further Information

Publication History

Received 29 June 2001

Accepted after resubmission 28 December 2001

Publication Date:
08 December 2017 (online)

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Summary

This investigation was undertaken to test whether anti-LBPA antibodies and IgG from patients with APS interfere with intracellular β2GPI distribution in EAhy926 endothelial cells and with the coagulation system. Cell incubation with anti-LBPA MoAb or with patients’ IgG resulted in antibody binding to late endosomes and caused β2GPI redistribution and accumulation within perinuclear vesicular structures reminiscent of late endosomes. This finding suggests that aPl may contribute to the pathogenic mechanisms of APS by modifying the intracellular traffic of proteins, by interactions between aPl and LBPA, β2GPI and/or LBPA- β2GPI complexes. The anticoagulant activity of anti-LBPA MoAb was analyzed in a sensitized activated partial thromboplastin time (aPTT) system and in a dilute Russell’s viper venom time (dRVVT). A significant, concentration-dependent effect of the antibody on both aPTT and dRVVT prolongation was found. These observations suggest that LBPA is an important lipid target for aPl with potential functional implications for the immunopathogenesis of APS.

Keywords

β2-glycoprotein I - late endosomes - endothelial cells - anti-phospholipid antibodies
 

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