Thrombus formation induced by antibodies to β2-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, Francesco Tedesco

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Abstract

We monitored the number of intravascular platelet-leukocyte aggregates (PLAs) and thrombotic occlusions (TOs) by intravascular microscopy in the mesentery of rats receiving antiphospholipid (aPL) immunoglobulin G (IgG) purified from the sera of patients with antiphospholipid syndrome. aPL IgG had no procoagulant effect, but it caused rapid endothelial deposition of fibrinogen, followed by PLA and TO in rats receiving an intraperitoneal injection of bacterial lipopolysaccharide 3 hours before IgG infusion. Anti-β2-glycoprotein I-depleted aPL IgG failed to induce PLAs and TOs. C3 and C9 colocalized with aPL IgG on the mesenteric vessels. The number of PLAs and TOs 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 β2-glycoprotein I trigger coagulation subsequent to a priming proinflammatory factor and that the terminal C complex is the main mediator of the coagulation process.

Original languageEnglish
Pages (from-to)2340-2346
Number of pages7
JournalBlood
Volume106
Issue number7
DOIs
Publication statusPublished - Oct 2005

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Antibody Formation
Glycoproteins
Platelets
Thrombosis
Immunoglobulin G
Antibodies
Rats
Leukocytes
Coagulation
Platelet Count
Blood Platelets
Complement Membrane Attack Complex
Antiphospholipid Antibodies
Mesentery
Antiphospholipid Syndrome
Intraperitoneal Injections
Leukocyte Count
Fibrinogen
Lipopolysaccharides
Microscopy

ASJC Scopus subject areas

  • Hematology

Cite this

Thrombus formation induced by antibodies to β2-glycoprotein I is complement dependent and requires a priming factor. / Fischetti, Fabio; Durigutto, Paolo; Pellis, Valentina; Debeus, Alessandra; Macor, Paolo; Bulla, Roberta; Bossi, Fleur; Ziller, Federica; Sblattero, Daniele; Meroni, Pierluigi; Tedesco, Francesco.

In: Blood, Vol. 106, No. 7, 10.2005, p. 2340-2346.

Research output: Contribution to journalArticle

Fischetti, F, Durigutto, P, Pellis, V, Debeus, A, Macor, P, Bulla, R, Bossi, F, Ziller, F, Sblattero, D, Meroni, P & Tedesco, F 2005, 'Thrombus formation induced by antibodies to β2-glycoprotein I is complement dependent and requires a priming factor', Blood, vol. 106, no. 7, pp. 2340-2346. https://doi.org/10.1182/blood-2005-03-1319
Fischetti, Fabio ; Durigutto, Paolo ; Pellis, Valentina ; Debeus, Alessandra ; Macor, Paolo ; Bulla, Roberta ; Bossi, Fleur ; Ziller, Federica ; Sblattero, Daniele ; Meroni, Pierluigi ; Tedesco, Francesco. / Thrombus formation induced by antibodies to β2-glycoprotein I is complement dependent and requires a priming factor. In: Blood. 2005 ; Vol. 106, No. 7. pp. 2340-2346.
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