The IgG and IgM isotypes of anti-annexin A5 antibodies: relevance for primary antiphospholipid syndrome

Bećarevic, Mirjana

doi:10.1007/s11239-016-1389-5

Cited by 22 publications

(14 citation statements)

References 40 publications

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“…Evaluation of sera from patients with APS as well as individuals with so- called ‘seronegative APS’ has revealed autoantibodies directed against several other antigenic targets including phosphatidylserine, phosphatidyl ethanolamine, annexin II, 43, 44 annexin A5, 45 and vimentin/cardiolipin complexes. 28, 39 However, the significance of these antibodies is not fully understood, since assays for their measurement are not standardized, their incidence in the general population is uncertain, and antibodies to some antigens such as vimentin/cardiolipin complexes may be common in patients with rheumatologic disease.…”

Section: Pathogenesis Of Apsmentioning

confidence: 99%

Diagnosis and management of the antiphospholipid syndrome

2017

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Antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy complications in the presence of persistent antiphospholipid antibodies (APLA). Laboratory diagnosis of APLA depends upon the detection of a lupus anticoagulant, which prolongs phospholipid-dependent anticoagulation tests, and/or anticardiolipin (aCL) and anti-β2-glycoprotein-1 (β2GPI) antibodies. APLA are primarily directed towards phospholipid binding proteins. Pathophysiologic mechanisms underlying thrombosis and pregnancy loss in APS include APLA induced cellular activation, inhibition of natural anticoagulant and fibrinolytic systems, and complement activation, among others. There is a high rate of recurrent thrombosis in APS, especially in triple positive patients (patients with lupus anticoagulants, aCL and anti-β2GPI antibodies), and indefinite anticoagulation with a vitamin K antagonist is the standard of care for thrombotic APS. There is currently insufficient evidence to recommend the routine use of direct oral anticoagulants (DOAC) in thrombotic APS. Aspirin with low molecular weight or unfractionated heparin may reduce the incidence of pregnancy loss in obstetric APS. Recent insights into the pathogenesis of APS have led to the identification of new potential therapeutic interventions, including anti-inflammatory and immunomodulatory therapies. Additional research is needed to better understand the effects of APLA on activation of signaling pathways in vascular cells, to identify more predictive biomarkers that define patients at greatest risk for a first or recurrent APLA-related clinical event, and to determine the safety and efficacy of DOACs and novel anti-inflammatory and immune-modulatory therapies for refractory APS.

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Section: Pathogenesis Of Apsmentioning

confidence: 99%

Diagnosis and management of the antiphospholipid syndrome

2017

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“…53 Antibodies against annexin A2 are associated with thrombosis, whereas annexin A5 antibodies were detected in women with pregnancy complications. 54 Autoantibodies against other coagulation system proteins, such as PS, PC, TFPI, and factors X, XI and XII, have been detected in subgroups of APS patients. Whether these antibodies play a causal role in the pathogenesis of APS is not clear; future prospective studies are required to clarify their potential to improve risk stratification of APS patients.…”

Section: Interpretation Of Apl Test Resultsmentioning

confidence: 99%

Laboratory Diagnostics in Thrombophilia

Linnemann

Hart

2019

Hamostaseologie

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A thrombophilic disorder is a hereditary or acquired condition that increases the risk of thrombosis. The most common hereditary thrombophilias that predispose to venous thrombosis in the Caucasian population are the heterozygous forms of the factor V Leiden and prothrombin G20210A mutation that are generally detected by direct DNA genotyping. Immunologic antigen assays and chromogenic or clot-based activity assays are used to identify deficiencies in the natural coagulation inhibitors antithrombin, protein C and protein S. Because pre-analytical errors and acquired causes of low antithrombin, protein C or protein S levels are considerably more common than hereditary deficiencies, all potential conditions that may lower activity levels of the natural coagulation inhibitors (e.g. concomitant liver disease, pregnancy, anticoagulant therapy) must be considered and excluded before the diagnosis of an inhibitor deficiency can be made. To avoid misclassification, the diagnosis should not be made based on a single abnormal test result. Thus, repetitive testing when the patient is not on anticoagulant therapy is mandatory to confirm the diagnosis. Screening for antiphospholipid syndrome (APS) comprises testing for lupus anticoagulants (LAs) and the presence of IgG or IgM antibodies directed against phospholipids and phospholipid-binding proteins such as β-2-glycoprotein-I. A combination of clot-based assays has been recommended to demonstrate LA activity, whereas solid-phase immunoassays allow the detection of anti-cardiolipin and anti-β-2-glycoprotein-I antibodies. The diagnosis of APS requires the persistence of antiphospholipid antibodies for at least 12 weeks together with thrombotic and/or obstetric features of APS.

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“…In contrast to aCL and aPS, the role of aAN in OAPS is yet controversial. The latter was linked with recurrent pregnancy morbidity and losses in some studies 35,45 but this association was not ascertained in others 41,46,47 . Still, the prediction of aPL related pregnancy morbidity is an issue of great debate, especially among women defined as "only aPLs carriers" or those with less than three early miscarriages.…”

Section: Discussionmentioning

confidence: 99%

Profiles of criteria and non-criteria anti-phospholipid autoantibodies are associated with clinical phenotypes of the antiphospholipid syndrome

Levin

Volkov

Seguro

et al. 2020

Preprint

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Background: Specific anti-phospholipids antibodies (aPLs) are used as classification criteria of the antiphospholipid syndrome (APS). These aPLs, although essential for diagnosis, do not predict disease phenotypes, which may require specific therapies. Non-criteria aPLs are rarely evaluated and their role is yet to be defined. In the current study, we aimed to examine the association between criteria and non-criteria aPLs and APS phenotypes.Methods: Serum samples from 188 subjects, 130 APS patients and 58 controls were analyzed for the presence of 20 aPLs (IgG and IgM isotypes to cardiolipin(CL), beta2-glycoprotein1(β2GP1), phosphatidic acid(P-acid), phosphatidylcholine(PC), phosphatidylethanolamine(PE), phosphatidylglycerol(PG), phosphatidylinositol(PI), phosphatidylserine(PS), annexin-5(AN) and prothrombin(PT) using a line immunoassay (GA Generic Assays, Germany). Sero-positivity to the different aPLs/aPLs profiles was correlated to APS phenotypes (i.e. arterial thrombosis, CNS manifestations, venous thrombosis, relapsing disease, obstetric morbidity). Results: In this cohort, arterial thrombosis was associated with accumulative number of ≥7/20 aPLs evaluated (OR 4.1; CI95% 1.9-96, p=0.001) as well as the sole presence of aPT(IgG) (OR 2.3;CI 95% 1.1-5.1, p=0.03). CNS manifestations were linked with a profile of 4 aPLs(IgG): aPT, aPG, aPI and aAN (OR 2.6;CI 95% 1.1-6.3, p=0.03). Symptom-free period of ≥3 years was linked with lower number of aPLs and the presence of aPI(IgG) (OR 3.0;CI 95% 1.08-8.1, p<0.05) or aAN(IgG) (OR 3.4;CI 95% 1.08-10.9, p<0.05). APS related pregnancy morbidity correlated with a profile of 2 aPLs(IgG): aCL and aPS (OR 2.9; CI95% 1.3-6.5, p<0.05) or the sole presence of aAN(IgG) (OR 2.8; CI95% 1.02-8, p=0.05). Conclusion: In this study, we observed an association between specific criteria/non-criteria aPLs or aPLs profiles and clinical phenotypes of APS. Our data suggest that examination of a wider variety of aPLs may allow better characterization of APS.

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The IgG and IgM isotypes of anti-annexin A5 antibodies: relevance for primary antiphospholipid syndrome

Cited by 22 publications

References 40 publications

Diagnosis and management of the antiphospholipid syndrome

Diagnosis and management of the antiphospholipid syndrome

Laboratory Diagnostics in Thrombophilia

Profiles of criteria and non-criteria anti-phospholipid autoantibodies are associated with clinical phenotypes of the antiphospholipid syndrome

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