P-058: Antiphospholipid antibodies and M2 haplotype in annexin A5 gene: possible relationship and clinical impact on feto-maternal outcome

2017 ◽  
Vol 151 ◽  
pp. S128
Author(s):  
M. Villani ◽  
E. Chinni ◽  
G.L. Tiscia ◽  
F. Cappucci ◽  
L. Fischetti ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Clinical Impact ◽  
Maternal Outcome ◽  
Annexin A5

Antiphospholipid Antibodies in a General Obstetric Population: Clinical Impact on Pregnancy Outcome and Relationship with the M2 Haplotype in the Annexin A5 (ANXA5) Gene

2018 ◽  
Vol 39 (02) ◽  
pp. 203-207
Author(s):  
Michela Villani ◽  
Donatella Colaizzo ◽  
Pasquale Martinelli ◽  
Filomena Cappucci ◽  
Lucia Fischetti ◽  
...  
Keyword(s):  
Risk Factors ◽  
Antiphospholipid Antibodies ◽  
Pregnancy Loss ◽  
Clinical Impact ◽  
Obstetric Complications ◽  
Obstetric Outcomes ◽  
P Value ◽  
Annexin A5 ◽  
Glycoprotein I ◽  
Obstetric Population

AbstractAntiphospholipid (aPL) antibodies are recognised risk factors for adverse obstetric outcomes. Recently, carriers of the M2 haplotype in the Annexin A5 gene have been shown to have a higher susceptibility to develop aPL antibodies. In a general obstetric population, we prospectively evaluated the possible relationship between: (1) aPL antibodies and M2 haplotype; and (2) aPL antibodies and/or M2 haplotype and obstetric outcomes. From a cohort of 3,097 consecutive pregnant women, 1,286 samples were analysed for the presence of both anti-cardiolipin and anti-human β2-glycoprotein I antibodies; samples with available DNA (n = 606) were also investigated for the M2 haplotype. Overall, 41/1,286 (3.2%) women showed the presence of aPL antibodies. Among them, 2 (4.8%) experienced a pregnancy loss and 38 (92.7%) gave birth to live-born babies (p-value = non-significant vs. those without aPL antibodies). M2 haplotype was identified in 140 (23.1%) out of 606 women with DNA available: 3/140 (2.1%) M2 carriers and 17/466 (3.6%) non-carriers tested positive for aPL antibodies, respectively (p-value = non-significant). In total, 15/150 (10%) M2 and/or aPL antibody carriers, and 38/445 (8.5%) non-aPL antibody and/or M2 carriers suffered from obstetric complications, respectively (p-value = non-significant). No relationship between aPL antibodies and M2 haplotype was found. Furthermore, neither aPL antibodies nor the M2 haplotype is associated with obstetric complications.

Correlation between antiphospholipid antibodies that recognize domain I of β2-glycoprotein I and a reduction in the anticoagulant activity of annexin A5

Blood ◽  
2006 ◽  
Vol 109 (4) ◽  
pp. 1490-1494 ◽  
Author(s):  
Bas de Laat ◽  
Xiao-Xuan Wu ◽  
Menno van Lummel ◽  
Ronald H. W. M. Derksen ◽  
Philip G. de Groot ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Anticoagulant Activity ◽  
Annexin A5 ◽  
Anionic Phospholipids ◽  
Glycoprotein I ◽  
Group A ◽  
Group B ◽  
Domain I ◽  
American Authors

Abstract The paradoxical correlation between thrombosis and the lupus anticoagulant (LAC) effect is an enigmatic feature of the antiphospholipid (aPL) syndrome. The Dutch authors previously reported that thrombosis-related anti–β2-glycoprotein I (β2GPI) antibodies recognize domain I and cause LAC. The American authors reported that aPLs disrupt an anticoagulant annexin A5 (AnxA5) crystal shield. We investigated whether antidomain I antibodies correlate with disruption of AnxA5-anticoagulant activity. We studied a well-characterized group of 33 patients including subgroups with β2GPI-dependent LAC that recognize domain I (n = 11), with β2GPI-independent LAC (n = 12), and lacking LAC (n = 10). The effects on AnxA5-anticoagulant activity were determined with an AnxA5 resistance assay that measures coagulation times with and without AnxA5. Patients with β2GPI-dependent LAC (group A, all with thrombosis) had significantly lower AnxA5-anticoagulant ratios than those with β2GPI-independent LAC (group B, thrombosis n = 4; 157.8% versus 235.6%, P < .001) and those without LAC (group C, thrombosis n = 2; 157.8% versus 232.5%, P < .001). There was no difference in the ratios between groups B and C (P = .92). Plasmas with β2GPI-dependent LAC that recognize domain I displayed significantly increased AnxA5 resistance, suggesting that specifically anti-β2GPI antibodies compete with AnxA5 for anionic phospholipids. These results are consistent with a model in which aPL antibodies may promote thrombosis by interfering with the anticoagulant activity of AnxA5.

scholarly journals Autoimmunity to the Lung Protective Phospholipid-Binding Protein Annexin A2 Predicts Mortality Among Hospitalized COVID-19 Patients

2021 ◽  
Author(s):  
Marisol Zuniga ◽  
Claudia Gomes ◽  
Steven E. Carsons ◽  
Michael T. Bender ◽  
Paolo Cotzia ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Binding Protein ◽  
Clinical Findings ◽  
Annexin A2 ◽  
P Value ◽  
Annexin A5 ◽  
Potential Mechanism ◽  
Membrane Stabilization ◽  
Phospholipid Binding ◽  
Antibody Levels

ABSTRACTBackgroundAnnexin A2 is a phospholipid-binding protein involved in fibrinolysis, cell membrane stabilization and repair, and ensuring the integrity of the pulmonary microvasculature. Given the autoantibodies observed in COVID-19 and that Annexin A2 is a known target of antiphospholipid antibodies, we studied autoimmunity directed against Annexin A2 among hospitalized COVID-19 patients.MethodsWe used ELISA to identify the levels of IgG autoantibodies recognizing Annexin A2 and A5 among 86 hospitalized cases of COVID-19. Using logistic regression, we analyzed the association between anti-Annexin A2 and A5 antibody levels with mortality after adjusting for age, sex, race and key comorbidities.ResultsWe found higher average levels of anti-Annexin A2 antibodies among hospitalized COVID-19 patients that died when compared with non-critical hospitalized COVID-19 patients (p-value = 0.006) and critically ill COVID-19 patients (p-value = 0.04). No significant differences in anti-Annexin A5 antibody levels were identified. Regression analysis showed that anti-Annexin A2 antibody levels as measured in relative units strongly predicted mortality with an odds ratio of 9.3 (95% CI: 1.9 to 44.6, p=0.005). In contrast, anti-Annexin A5 antibody levels were not associated with higher mortality (95% CI: 0.5 to 15.2, p=0.22).ConclusionsWe determined that anti-Annexin A2 antibodies were elevated among hospitalized COVID-19 patients and these levels predicted mortality. It is known that inhibition of Annexin A2 induces systemic thrombosis, cell death, and non-cardiogenic pulmonary edema. Autoimmunity to Annexin A2 is a potential mechanism that may explain the key clinical findings of severe COVID-19.

Pathogenic antiphospholipid antibody: an antigen-selected needle in a haystack

Blood ◽  
2004 ◽  
Vol 104 (6) ◽  
pp. 1711-1715 ◽  
Author(s):  
Patricia Lieby ◽  
Vincent Poindron ◽  
Stamatiki Roussi ◽  
Cyril Klein ◽  
Anne-Marie Knapp ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Germ Line ◽  
Annexin A5 ◽  
Antiphospholipid Antibody ◽  
Variable Regions ◽  
Anionic Phospholipids ◽  
Pregnant Mice

Abstract Antiphospholipid antibodies represent a heterogeneous group of autoantibodies directed against anionic phospholipids (PLs) usually linked to protein cofactors. Their presence during the antiphospholipid syndrome is associated with risks of thrombosis and fetal losses. Among 5 randomly selected monoclonal antiphospholipid antibodies, all originating from a single patient suffering from this autoimmune disease, only 1 induced fetal losses when passively injected into pregnant mice. Its antiphospholipid activity was dependent on annexin A5, and its variable regions contained mainly 3 replacement mutations. To clarify the role of these mutations in the pathogenicity of the antibody, they were in vitro reverted to the germ line configuration. The resulting “germ line” antibody reacted with multiple self-antigens and only partially lost its reactivity against PLs, but it was no more dependent on annexin A5 and, more importantly, was no more pathogenic. This study illustrates that the in vivo antigen-driven maturation process of natural autoreactive B cells can be responsible for pathogenicity. (Blood. 2004;104:1711-1715)

Anti-annexin A5 Antibodies in Reproductive Failures in Relation to Antiphospholipid Antibodies and Phosphatidylserine

2003 ◽  
Vol 50 (3) ◽  
pp. 202-208 ◽  
Author(s):  
T. Arai ◽  
H. Matsubayashi ◽  
T. Sugi ◽  
A. Kondo ◽  
M. Shida ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Annexin A5

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.

scholarly journals Non-criteria Antiphospholipid Antibodies: a narrative review

2020 ◽  
Vol 66 (11) ◽  
pp. 1595-1601
Author(s):  
Andreas Funke ◽  
Henrique Luiz Staub ◽  
Odirlei Andre Monticielo ◽  
Gustavo Guimarães Moreira Balbi ◽  
Adriana Danowski ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Laboratory Diagnosis ◽  
Diagnostic Value ◽  
Classification Criteria ◽  
Narrative Review ◽  
Annexin A5 ◽  
Clinical Associations ◽  
Domain I

SUMMARY The 2006 Revised Sapporo Classification Criteria for Definite Antiphospholipid Syndrome included as laboratory criteria the tests for antiphospholipid antibodies whose accuracy was regarded as satisfactory according to the evidence available at that time. In practice, however, the sensitivity and specificity of these “criteria” of antiphospholipid antibodies are sometimes insufficient for identifying or ruling out antiphospholipid syndrome. It has been studied whether the accuracy of the laboratory diagnosis of the syndrome could be improved by testing for non-criteria antiphospholipid antibodies. In this work, we review evidence on the clinical associations and diagnostic value of the most commonly studied non-criteria antibodies, namely: antiphosphatidylethanolamine, anti-annexin A5, anti-prothrombin, anti-phosphatidylserine/prothrombin complex, IgA anticardiolipin, and IgG anti-domain I of the β2 glycoprotein antibodies.

scholarly journals Apoptosis, Annexin A5 and Anti-Annexin A5 Antibodies in The Antiphospholipid Syndrome

2013 ◽  
Vol 32 (2) ◽  
pp. 89-95 ◽  
Author(s):  
Mirjana Bećarević ◽  
Svetlana Ignjatović ◽  
Nada Majkić-Singh
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Imaging Techniques ◽  
Annexin A5 ◽  
Primary Antiphospholipid Syndrome ◽  
History Of ◽  
Recurrent Abortions ◽  
And Function

Summary It has been proposed that apoptosis is one of the mechanisms involved in the generation of antiphospholipid antibodies. The presence of antiphospholipid antibodies is the main laboratory criterion for a definite diagnosis of the antiphospholipid syndrome. Annexinopathies are disorders characterized by deregulation of annexins expression levels and function. Annexin A5 has been used as an agent for molecular imaging techniques (visualization of phosphatidylserineexpressing apoptotic cells) in vitro and in vivo in animal models and in patients (injection of human recombinant anxA5 into the patient‘s circulation). Although the determination of titers of anti-annexin A5 antibodies is not mandatory for the diagnosis of the antiphospholipid syndrome, it was reported that patients with primary antiphospholipid syndrome with a history of recurrent abortions had elevated titers of antiannexin A5 antibodies, while the presence of thromboses was not associated with elevated levels of these antibodies

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