Faculty Opinions recommendation of Annexin A5 anticoagulant activity in children with systemic lupus erythematosus and the association with antibodies to domain I of β2-glycoprotein I.

2016 ◽  
Author(s):  
Maria Laura Bertolaccini
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Anticoagulant Activity ◽  
Annexin A5 ◽  
Systemic Lupus ◽  
Glycoprotein I ◽  
Domain I

Inhibition of Lupus Anticoagulant Activity by Hexagonal Phase Phosphatidylethanolamine in the Presence of Prothrombin

1998 ◽  
Vol 80 (12) ◽  
pp. 936-941 ◽  
Author(s):  
Marion Tannenbaum ◽  
Carolyn Neville ◽  
Paul Fortin ◽  
Joyce Rauch
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Lupus Anticoagulant ◽  
Plasma Proteins ◽  
Anticoagulant Activity ◽  
Hexagonal Phase ◽  
Annexin V ◽  
Systemic Lupus ◽  
Glycoprotein I ◽  
No Inhibition

SummaryWe have previously demonstrated that lupus anticoagulant antibodies from patients with systemic lupus erythematosus (SLE) specifically recognize hexagonal (II) phase phosphatidylethanolamine (PE), but not bilayer PE (Thromb Haemost 1989; 62: 892). In those studies, the involvement of proteins in this recognition was not evaluated. To address this issue, we have isolated IgG lupus anticoagulant antibodies from the plasma of SLE patients and evaluated the inhibition of lupus anticoagulant activity by hexagonal (II) phase PE in the presence and absence of purified plasma proteins. All six of the IgG lupus anticoagulant antibodies tested were inhibited by hexagonal (II) phase PE in the presence, but not the absence, of human prothrombin. In contrast, little or no inhibition was observed with prothrombin alone or with PE in combination with either β2-glycoprotein I or annexin V. These data indicate that, for certain lupus anticoagulant antibodies, inhibition by hexagonal (II) phase PE is dependent on prothrombin, suggesting that these antibodies recognize a complex of PE and prothrombin.

Prevalence of Annexin A5 Resistance in Children and Adolescents with Rheumatic Diseases

2011 ◽  
Vol 39 (2) ◽  
pp. 382-388 ◽  
Author(s):  
DAWN M. WAHEZI ◽  
NORMAN T. ILOWITE ◽  
SWAPNIL RAJPATHAK ◽  
JACOB H. RAND
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Connective Tissue ◽  
Children And Adolescents ◽  
Rheumatic Diseases ◽  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Anticoagulant Activity ◽  
Underlying Mechanism ◽  
Annexin A5 ◽  
Systemic Lupus

Objective.The underlying mechanism(s) by which antiphospholipid antibodies (aPL) result in thrombosis remains poorly understood. A significant body of evidence has evolved to support the hypothesis that antibody-mediated disruption of an annexin A5 anticoagulant shield may play a role in the pathogenesis; this proposed mechanism has not been previously studied in children.Methods.We investigated the association between aPL and resistance to annexin A5 anticoagulant activity in 90 children with a variety of rheumatic diseases using a novel mechanistic assay, the annexin A5 resistance assay (A5R).Results.Patients with a diagnosis of primary aPL syndrome, systemic lupus erythematosus, and mixed connective tissue disease demonstrated lower mean A5R levels (p = 0.030), higher prevalence of positive aPL (p < 0.001), and more thrombotic events (p = 0.014) compared to those with other diagnoses. Patients with persistently positive aPL had significantly lower mean A5R compared to patients with no aPL (mean A5R = 203% ± 44% vs 247% ± 35%; p < 0.001), whereas patients with transient aPL did not. Patients with thrombosis had lower A5R levels compared to those without thrombosis (mean A5R = 207% ± 36% vs 237% ± 46%; p = 0.048).Conclusion.Children and adolescents with rheumatic diseases and persistent aPL have reduced annexin A5 anticoagulant activity, whereas transient, nonpathogenic aPL have less effect on annexin A5 activity.

Autoantibodies specific to a peptide of β2-glycoprotein I cross-react with TLR4, inducing a proinflammatory phenotype in endothelial cells and monocytes

Blood ◽  
2012 ◽  
Vol 120 (16) ◽  
pp. 3360-3370 ◽  
Author(s):  
Tania Colasanti ◽  
Cristiano Alessandri ◽  
Antonella Capozzi ◽  
Maurizio Sorice ◽  
Federica Delunardo ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Endothelial Cells ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Interleukin 1 ◽  
Pathogenic Mechanism ◽  
Hek293 Cells ◽  
Systemic Lupus ◽  
Glycoprotein I ◽  
Domain I

Abstractβ2-glycoprotein I (β2GPI) is the major antigenic target for antiphospholipid Abs. Anti-β2GPI Abs are a heterogeneous population of Igs targeting all domains of the molecule. Abs specific to β2GPI domain I are strongly associated with thrombosis and obstetric complications. In the present study, we sought to understand the possible pathogenic mechanism for this subset of anti-β2GPI Abs, investigating their potential cross-reactivity with other self-proteins involved in inflammatory or coagulant events. We compared the amino acid sequence of the β2GPI domain I with human proteins in a protein databank and identified a peptide sharing 88% identity with an epitope of human TLR4. A high percentage of patients with antiphospholipid syndrome (41%) and systemic lupus erythematosus (50%) presented serum IgG specific to this peptide. Anti-β2GPI peptide Abs binding the TLR4 were able to induce NF-κB activation in HEK293 cells that were stably transfected with the TLR4 gene. Anti-β2GPI peptide Abs induced activation of TLR4 and triggered interleukin-1 receptor-associated kinase phosphorylation and NF-κB translocation, promoting VCAM expression on endothelial cells and TNF-α release by monocytes. In conclusion, our observations suggest a novel pathogenic mechanism in the TLR4 stimulation by anti-β2GPI peptide Abs that links adaptive immune responses with innate immunity in antiphospholipid syndrome and systemic lupus erythematosus.

The Coagulation Abnormalities in Systemic Lupus Erythematosus

1968 ◽  
Vol 20 (03/04) ◽  
pp. 457-464 ◽  
Author(s):  
L Gonyea ◽  
R Herdman ◽  
R. A Bridges
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Ammonium Sulfate ◽  
Lupus Erythematosus ◽  
Anticoagulant Activity ◽  
Species Specificity ◽  
Sensitive Assay ◽  
Systemic Lupus ◽  
Coagulation Abnormalities

SummaryAn anticoagulant occurring in 4 of 6 patients with SLE has been demonstrated by a sensitive assay utilizing an ammonium sulfate fraction of serum. The anticoagulant functions as an inhibitor of the activation of prothrombin. No species specificity was demonstrable. The inhibitor behaves clinically and chromatographically as an immunoglobulin, although an attempt to demonstrate directly the antibody nature of the inhibitor was not successful.A severe, apparently independent, decrease in the level of prothrombin was observed in the patient with hemorrhagic symptoms. In contrast to the anticoagulant activity, the low prothrombin has persisted during treatment.

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