Clinical utility of anticardiolipin antibody assays: high inter-laboratory variation and limited consensus by participants of external quality assurance programs signals a cautious approach

Favaloro, Emmanuel J.; Silvestrini, Roger; Mohammed, Ali

doi:10.1080/003130299105331

Cited by 49 publications

(50 citation statements)

References 10 publications

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“…There has been considerable difficulty in generating reliable and reproducible clinical assays for measuring aCL, 25,26 which we believe is partly because of the oxidation of CL. In fact, there is variability not only between different preparations but even in the same CL preparation depending on its "age" (even if stored at Ϫ70°C under argon).…”

Section: Discussionmentioning

confidence: 99%

Anticardiolipin Antibodies From Patients With the Antiphospholipid Antibody Syndrome Recognize Epitopes in Both β ₂ -Glycoprotein 1 and Oxidized Low-Density Lipoprotein

Hörkkö

Olee

et al. 2001

Circulation

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Background-We recently suggested that many anticardiolipin antibodies bind only to oxidized cardiolipin (OxCL) and/or to OxCL-␤ 2 -glycoprotein 1 (␤ 2 GP1) adducts but not to a "reduced" cardiolipin that is unable to undergo oxidation. To test this hypothesis, we investigated 24 sera, 4 protein A-purified IgG fractions, and 3 human monoclonal antibodies that were all isolated from patients with antiphospholipid antibody syndrome (APS); testing was also performed in 7 controls. Two monoclonal antibodies (IS3 and IS4) were selected for binding to CL and one was selected for binding to ␤ 2 GP1 (LJB8). Methods and Results-By chemiluminescent immunoassay, all APS sera samples bound only to OxCL and not to reduced CL, and the binding was inhibited Ͼ95% by OxCL but not reduced CL. All purified IgG fractions bound to ␤ 2 GP1 but only when the ␤ 2 GP1 was plated on microtiter wells coated with OxCL. All 3 monoclonal antibodies bound only to OxCL. On Western blots, IS4 and LJB8 bound to ␤ 2 GP1 as well as to delipidated apoB of oxidized LDL but not to native apoB. IS3 also bound to oxidized apoB on Western blot. Covalent modification of ␤ 2 GP1 with oxidation products of CL made it more antigenic for APS serum samples, for purified IgG fractions, and for the monoclonal antibodies. Conclusions-These data support the hypothesis that oxidation of CL is needed to generate epitopes for many anticardiolipin antibodies and that some of these epitopes are covalent adducts of OxCL with ␤ 2 GP1 or apoB.

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Section: Discussionmentioning

confidence: 99%

Anticardiolipin Antibodies From Patients With the Antiphospholipid Antibody Syndrome Recognize Epitopes in Both β ₂ -Glycoprotein 1 and Oxidized Low-Density Lipoprotein

Hörkkö

Olee

et al. 2001

Circulation

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“…Although the cited studies used an average of multiple test results from the same laboratory, 102,103 the potential for interlaboratory variability was not addressed. 94 On the basis of these methodological issues, the posttest probabilities calculated in this study should be viewed as rough estimates.…”

Section: Discussionmentioning

confidence: 99%

“…95 The significance of IgM titers is also unclear because they may be elevated in diseases other than stroke. 80 Second, the diagnosis of ACL or LA positivity must be confirmed with repeated testing 3,94 since another important feature of ACL and LA is that the titers can fluctuate over time. 96,97 Only 2 studies 87,88 mentioned confirmation of abnormal titers.…”

Section: Anticardiolipin Antibodies/lupus Anticoagulantmentioning

confidence: 99%

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Diagnostic Testing for Coagulopathies in Patients With Ischemic Stroke

Bushnell

Goldstein

2000

Stroke

152

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Background-Hypercoagulable states are a recognized, albeit uncommon, etiology of ischemic stroke. It is unclear how often the results of specialized coagulation tests affect management. Using data compiled from a systematic review of available studies, we employed quantitative methodology to assess the diagnostic yield of coagulation tests for identification of coagulopathies in ischemic stroke patients. Summary of Review-We performed a MEDLINE search to identify controlled studies published during 1966 -1999 that reported the prevalence of deficiencies of protein C, protein S, antithrombin III, plasminogen, activated protein C resistance (APCR)/factor V Leiden mutation (FVL), anticardiolipin antibodies (ACL), or lupus anticoagulant (LA) in patients with ischemic stroke. The cumulative prevalence rates (pretest probabilities) and positive likelihood ratios for all studies and for those including only patients aged Յ50 years were used to calculate posttest probabilities for each coagulopathy, reflecting diagnostic yield. The cumulative pretest probabilities of coagulation defects in ischemic stroke patients are as follows: LA, 3% (8% for those aged Յ50 years); ACL, 17% (21% for those aged Յ50 years); APCR/FVL, 7% (11% for those aged Յ50 years); and prothrombin mutation, 4.5% (5.7% for those aged Յ50 years). The posttest probabilities of ACL, LA, and APCR increased with increasing pretest probability, the specificity of the tests, and features of the patients' history and clinical presentation. Conclusions--The pretest probabilities of coagulation defects in ischemic stroke patients are low. The diagnostic yield of coagulation tests may be increased by using tests with the highest specificities and by targeting patients with clinical or historical features that increase pretest probability. Consideration of these data might lead to more rational ordering of tests and an associated cost savings. (Stroke. 2000;31:3067-3078.)

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“…Standardization of the aCL enzyme-linked immunosorbent assay (ELISA), which proved difficult (18)(19)(20), began with the introduction of standards based on patient sera, such as the widely used Kingston Antiphospholipid Study (KAPS) samples (18 (21)(22)(23)(24)(25) and make generalization of a specific, clinically relevant cutoff (26) hazardous. The fact that many important studies on the treatment of obstetric APS (27)(28)(29)(30)(31)(32) evoked letters to the editor (33-39) disputing their reported cutoffs in the aCL ELISA illustrates that consensus is urgently needed.…”

Section: The Obstetric Apsmentioning

confidence: 99%

Management of the obstetric antiphospholipid syndrome

Derksen¹,

Khamashta²,

Branch³

2004

Arthritis & Rheumatism

185

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Clinical utility of anticardiolipin antibody assays: high inter-laboratory variation and limited consensus by participants of external quality assurance programs signals a cautious approach

Cited by 49 publications

References 10 publications

Anticardiolipin Antibodies From Patients With the Antiphospholipid Antibody Syndrome Recognize Epitopes in Both β ₂ -Glycoprotein 1 and Oxidized Low-Density Lipoprotein

Anticardiolipin Antibodies From Patients With the Antiphospholipid Antibody Syndrome Recognize Epitopes in Both β ₂ -Glycoprotein 1 and Oxidized Low-Density Lipoprotein

Diagnostic Testing for Coagulopathies in Patients With Ischemic Stroke

Management of the obstetric antiphospholipid syndrome

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Clinical utility of anticardiolipin antibody assays: high inter-laboratory variation and limited consensus by participants of external quality assurance programs signals a cautious approach

Cited by 49 publications

References 10 publications

Anticardiolipin Antibodies From Patients With the Antiphospholipid Antibody Syndrome Recognize Epitopes in Both β 2 -Glycoprotein 1 and Oxidized Low-Density Lipoprotein

Anticardiolipin Antibodies From Patients With the Antiphospholipid Antibody Syndrome Recognize Epitopes in Both β 2 -Glycoprotein 1 and Oxidized Low-Density Lipoprotein

Diagnostic Testing for Coagulopathies in Patients With Ischemic Stroke

Management of the obstetric antiphospholipid syndrome

Contact Info

Product

Resources

About

Anticardiolipin Antibodies From Patients With the Antiphospholipid Antibody Syndrome Recognize Epitopes in Both β ₂ -Glycoprotein 1 and Oxidized Low-Density Lipoprotein

Anticardiolipin Antibodies From Patients With the Antiphospholipid Antibody Syndrome Recognize Epitopes in Both β ₂ -Glycoprotein 1 and Oxidized Low-Density Lipoprotein