Antibodies to platelets in patients with anti-phospholipid antibodies

Out, HJ; Groot, PG de; Vliet, Mariska van; Gast, GC de; Nieuwenhuis, H. K.; Rh, Derksen

doi:10.1182/blood.v77.12.2655.bloodjournal77122655

Cited by 6 publications

(8 citation statements)

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“…APL antibodies also induce platelet activation and interact with elements of the coagulation cascade. 8,9,[10][11][12][13][14][15] This activity, however, does not seem to be sufficient to cause thrombosis. Activation of the complement cascade by aPL may amplify these effects by stimulation of the generation of potent mediators of platelet and endothelial cell activation, including C3a and C5a and the C5b-MAC.…”

Section: Discussionmentioning

confidence: 99%

“…6,7 In fact, in vitro studies have reported that aPL may cause thrombosis by interfering with activation of protein C (or inactivation of factor V by activated protein C), inhibit endothelial prostacyclin production, impair fibrinolysis, and exert stimulatory effect on platelet function. [6][7][8][9][10][11][12][13][14][15][16][17][18][19] Recently convincing evidence has shown that activation of complement mediates thrombogenic effects of aPL and fetal loss in APS. [20][21][22][23][24] This paper discusses specifically those new and exciting findings with respect to the involvement of the complement cascade in pathogenic effects of aPL antibodies.…”

Section: Introductionmentioning

confidence: 99%

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Complement Activation: A Novel Pathogenic Mechanism in the Antiphospholipid Syndrome

Pierangeli¹,

Vega-Ostertag²,

Liu³

et al. 2005

Annals of the New York Academy of Sciences

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Antiphospholipid antibodies (aPLs) have been shown to induce thrombosis, activate endothelial cells, and induce fetal loss. The pathogenesis of aPL-induced thrombosis is incompletely understood, but it is thought to involve platelet and endothelial cell activation as well as pro-coagulant effects of aPL antibody directly on clotting pathway components. Recent studies have shown that uncontrolled complement activation leads to fetal death in aPL-antibody treated mice. We hypothesized that aPL antibodies activate complement, generating split products that induce thrombosis. To test this hypothesis, we used an in vivo model of thrombosis in which aPL antibodies induce a significant increase in thrombus size and a mouse model of endothelial cell activation in which aPLs induce significant adhesion of leukocytes (WBCs) to endothelial cells. We found that mice deficient in complement components C3 and C5 were resistant to enhanced thrombosis and endothelial cell activation induced by aPL antibodies. Furthermore, inhibition of C5 activation using anti-C5 mAb prevented thrombophilia induced by aPL antibodies. Our data show that complement activation mediates two important effectors of aPL antibodies: induction of thrombosis and endothelial activation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Complement Activation: A Novel Pathogenic Mechanism in the Antiphospholipid Syndrome

Pierangeli¹,

Vega-Ostertag²,

Liu³

et al. 2005

Annals of the New York Academy of Sciences

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“…Elsewhere, an imbalance between the synthesis of thromboxane and prostaglandin I 2 has been reported in patients with lupus anticoagulant ( Lellouche et al , 1991 ). Other studies have failed to confirm that platelets circulate in an activated state in patients who display platelet binding anti‐phospholipid antibodies ( Out et al , 1991 ).…”

Section: Discussionmentioning

confidence: 99%

“…There is evidence that platelet microparticles and activated platelets are present in the circulation in certain thrombotic disease states ( Abrams et al , 1990 ; Michelson, 1996), as well as in patients with antiphospholipid antibodies ( Galli et al , 1993b ). Some recent studies, using flow cytometry to detect the expression of platelet activation markers, have indicated that patients with the antiphospholipid syndrome have circulating activated platelets ( Fanelli et al , 1997 ; Galli et al , 1993b ; Joseph et al , 1997 ), although this has not been a consistent finding ( Out et al , 1991 ). It is unclear, however, whether ‘antiphospholipid’ antibodies are capable of initiating platelet activation, or if other components and conditions are required.…”

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confidence: 99%

IgG from patients with antiphospholipid syndrome binds to platelets without induction of platelet activation

1998

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Summary.The clinical manifestations of the antiphospholipid syndrome (APLS) include arterial and venous thrombosis, thrombocytopenia and fetal loss, but the pathogenic mechanisms remain unclear. It has been hypothesized that platelet activation by autoantibody may be a pathogenic mechanism. We studied IgG binding, microparticle (mp) formation and P-selectin expression by flow cytometry in normal platelets after incubation in serum from 11 patients with antiphospholipid antibodies and that from 10 normal healthy subjects. Levels of platelet-associated IgG were significantly higher after incubation in patient sera (mean 17·2, range 2·0-75·0%) compared with normal sera (mean 2·0, range 1·2-3·7%, P < 0·05). Incubation of normal platelets in serum led to increased microparticle formation (P < 0·01) and P-selectin expression (P < 0·05), compared with unstimulated platelets. There was no significant difference, however, between microparticle formation nor P-Selectin expression induced by patient serum (mp 3·0 (1·6-5·0)%; P-selectin 8·0 (4·0-16·6)%) versus normal serum (mp 3·2 (2·1-4·5)%; P-selectin 10·1 (4·0-15·6); median (range)). Pre-activation of platelets with subthreshold ADP concentrations or thrombin receptor activator peptide resulted in a small increase in microparticle formation, but there was still no significant difference between the effects of patient and control sera. Despite the presence of platelet membrane binding IgG in serum from 5/11 patients with antiphospholipid antibodies, there was no evidence for associated enhanced platelet-activating ability. This study supports antiplatelet reactivity in antiphospholipid syndrome, but not a direct platelet-activating role for platelet-directed autoantibodies.

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“…It is commonly used in the diagnosis of clinical conditions such as acute leukaemia and human immunodeficiency virus. Its versatility as a tool for identification of cell surface antigens has also enabled the study of antiplatelet antibodies (11). Monoclonal antibodies have been used to identify platelet activation in immune thrombocytopaenia (12,13), as well as in patients following cardiopulmonary bypass and in hypercoagulable states (14)(15)(16).…”

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confidence: 99%

Detection of anti-phosphatidylethanolamine antibodies using flow cytometry

1999

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Background: The finding that lupus anticoagulant (LA) is significantly associated with anti‐phosphatidylethanolamine (PE) activity has led to great interest in its relation to the clinical features of the antiphospholipid syndrome (APS). Considerable variability has, however, been reported in the prevalence of anti‐PE antibodies in APS patients using enzyme‐linked immunosorbent assay (ELISA) methodology. The lack of standardization and differences in technique may in part explain these discrepancies. PE binds variably to different types of microtiter wells, reflected in the consequent detection, or lack of detection, of anti‐PE antibodies. This study describes the use of flow cytometry as an alternative method for the detection of anti‐PE antibodies. Methods: Six LA‐positive plasma samples were used in this original study. Polystyrene beads were coated with PE overnight. These were subsequently incubated with patient plasma. Both IgG and IgM binding were detected by flow cytometry using a cocktail of fluorescently labelled anti‐human Ig isotypes. Results: When these results were compared with those from ELISA, flow cytometric analysis provided an apparent enhanced detection of anti‐PE antibodies. It was found that 6/6 were IgM anti‐PE positive by flow cytometry, whereas 5/6 were IgM by ELISA; 2/6 negative for anti‐cardiolipin antibodies by ELISA were positive by flow cytometry; and 2/6 positive for antiphosphatidylcholine antibodies in cytometry were negative by ELISA. Conclusions: With appropriate quantification, this method may be more sensitive than ELISA in detecting anti‐PE antibodies in plasma samples of patients with APS. Cytometry 36:46–51, 1999. © 1999 Wiley‐Liss, Inc.

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Antibodies to platelets in patients with anti-phospholipid antibodies

Cited by 6 publications

References 0 publications

Complement Activation: A Novel Pathogenic Mechanism in the Antiphospholipid Syndrome

Complement Activation: A Novel Pathogenic Mechanism in the Antiphospholipid Syndrome

IgG from patients with antiphospholipid syndrome binds to platelets without induction of platelet activation

Detection of anti-phosphatidylethanolamine antibodies using flow cytometry

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