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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2340-2346.
Prepublished online as a Blood First Edition Paper on June 14, 2005; DOI 10.1182/blood-2005-03-1319.
 Previous Article | Next Article 
Submitted March 31, 2005
Accepted June 3, 2005
Thrombus formation induced by antibodies to  2-glycoprotein I is complement-dependent and requires a priming factor
Fabio Fischetti, Paolo Durigutto, Valentina Pellis, Alessandra Debeus, Paolo Macor, Roberta Bulla, Fleur Bossi, Federica Ziller, Daniele Sblattero, Pierluigi Meroni, and Francesco Tedesco*
Department of Physiology and Pathology, University of Trieste, Trieste, Italy; Department of Medicine and Neurology, University of Trieste, Trieste, Italy
Department of Physiology and Pathology, University of Trieste, Trieste, Italy
Department of Medical Sciences, University of Eastern Piedmont, Novara, Italy
Department of Internal Medicine, Allergy and Clinical Immunology Section, IRCCS Istituto Auxologico Italiano, University of Milan, Milan, Italy
* Corresponding author; email: tedesco{at}univ.trieste.it.
We monitored the number of intravascular platelet-leukocyte aggregates (PLA) and thrombotic occlusions (TO) by intravascular microscopy in the mesentery of rats receiving antiphospholipid (aPL) immunoglobulin (Ig)G purified from the sera of patients with antiphospholipid syndrome. aPL IgG had no procoagulant effect, but caused rapid endothelial deposition of fibrinogen, followed by PLA and TO in rats receiving an intraperitoneal injection of bacterial lipopolysaccharide 3 h before IgG infusion. Anti- 2-glycoprotein I-depleted aPL IgG failed to induce PLA and TO. C3 and C9 co-localized with aPL IgG on the mesenteric vessels. The number of PLA and TO was markedly reduced in C6-deficient rats and in animals treated with anti-C5 miniantibody suggesting the contribution of the terminal complement (C) complex to the aPL antibody-mediated intravascular thrombosis. In conclusion, our data indicate that antibodies to 2-glycoprotein I trigger coagulation subsequent to a priming pro-inflammatory factor and that the terminal C complex is the main mediator of the coagulation process.
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