Optimising testing for phospholipid antibodies

Helbert, Matthew; Bodger, Stephen; Cavenagh, J; D’Cruz, David; Thomas, John; MacCallum, Peter

doi:10.1136/jcp.54.9.693

Cited by 21 publications

(20 citation statements)

References 22 publications

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“…h 2 GPI constitutes the major antigenic target for aPL circulating in the serum of APS patients [6]; therefore, the term ''antiphospholipid antibodies'' is actually a misnomer. It is currently evident that the h 2 GPI ELISA has greater specificity and positive predictive value than the cardiolipin ELISA for the diagnosis of clinically significant APS [7,8]. These data confirmed previous experimental results on the role of h 2 GPI-dependent aPL in distinguishing between APS occurring in the setting of autoimmune diseases and the transient occurrence of aPL associated with infections [9].…”

Section: Introductionsupporting

confidence: 80%

Beta-2 glycoprotein I and its role in antiphospholipid syndrome—lessons from knockout mice

Miyakis

Robertson

Krilis

2004

Clinical Immunology

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The antiphospholipid syndrome is characterized by the presence in serum of autoantibodies against h2GPI. Although the role of h2GPI in the pathogenesis of antiphospholipid antibody syndrome (APS) is well recognized, its exact physiological functions still remain undisclosed. Several interactions of h2GPI with components of the coagulation cascade have been proposed, resulting in both procoagulant and anticoagulant effects. Additionally, h2GPI has been implicated in the mechanism of recurrent fetal loss entailed in APS. Recently, using a homologous recombination approach, reproduction of mice homozygous for deletion of the b2GPI gene has been feasible. h2GPI knockout mice offer a valuable tool for revealing the physiological role of the protein. These mice show decreased in vitro ability for thrombin generation. Furthermore, although mice lacking h2GPI are fertile, the success of early pregnancy is moderately compromised and functional h2GPI is believed necessary for optimal implantation and placental morphogenesis. AbstractThe antiphospholipid syndrome is characterized by the presence in serum of autoantibodies against h 2 GPI. Although the role of h 2 GPI in the pathogenesis of antiphospholipid antibody syndrome (APS) is well recognized, its exact physiological functions still remain undisclosed. Several interactions of h 2 GPI with components of the coagulation cascade have been proposed, resulting in both procoagulant and anticoagulant effects. Additionally, h 2 GPI has been implicated in the mechanism of recurrent fetal loss entailed in APS. Recently, using a homologous recombination approach, reproduction of mice homozygous for deletion of the b 2 GPI gene has been feasible. h 2 GPI knockout mice offer a valuable tool for revealing the physiological role of the protein. These mice show decreased in vitro ability for thrombin generation. Furthermore, although mice lacking h 2 GPI are fertile, the success of early pregnancy is moderately compromised and functional h 2 GPI is believed necessary for optimal implantation and placental morphogenesis. D

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Section: Introductionsupporting

confidence: 80%

Beta-2 glycoprotein I and its role in antiphospholipid syndrome—lessons from knockout mice

Miyakis

Robertson

Krilis

2004

Clinical Immunology

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“…Solid phase immunoassay is performed on human 132-GPl-coated plates, usually in the presence of bovine serum 132-glycoprotein I [6]. Although their presence is not currently i ncluded in the criteria for the APS [1], 132-GP1 antibody assays show higher precision and better correlation with the thromboembolic complieations in APS and SLE than assays for aCL and are less likely to show transient positive results in association with infection [46,47]. However, the problem of standardizatiDn remain.…”

Section: Anti-fl2-gtycoprotein 1 (Anti-fl2gp1) Antibodiesmentioning

confidence: 98%

“…Human 132-glycoprotein 1 is a plasma glycoprotein that can actas a physiological anticoagulant, in vitro at least, inhibiting the clotting cascade and platelet aggregation [46]. 132-GP1 is required asa cofactor for the binding of aCL to cardiolipin in APS, but not in infection.…”

Section: Anti-fl2-gtycoprotein 1 (Anti-fl2gp1) Antibodiesmentioning

confidence: 99%

Recent advances in the diagnosis of antiphospholipid syndrome

Chi

2002

Int J Hematol

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Antiphospholipid antibodies are autoantibodies directed against anionic phospholipids or protein-phospholipid complexes measured in solid-phase immunoassays such as anticardiolipin (aCL) antibody or detected in phospholipid-dependent clotting tests as lupus anticoagulant (LA). The term "antiphospholipid syndrome (APS)" was first coined to denote the clinical association between antiphospholipid antibodies and a syndrome of episodes of thrombosis in arteries and/or veins, pregnancy loss, and thrombocytopenia. The diagnosis of APS is based on the finding of "moderate-to-high" aCL antibody titer and/or an LA test with any one of the characteristic clinical features presented. Recently, the diagnostic criteria of APS was revised and several newer assays that use phosphatidylserine, a mixture of negatively charged phospholipids or beta2-glycoprotein 1 (beta2-GP1) have been proposed for more specific measurements of antibodies present in APS. In this section, recent progress in the laboratory diagnosis of antiphopholipid syndrome will be discussed.

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“…Partially prompted by this change, a number of APS experts have therefore recommended that the aCL test be completely abandoned and replaced by the anti-β2GPI test, in order to reduce the potential number of these false-positive (largely β2GPI independent) aCL test results [17,42]. However, while the anti-β2GPI assay is more specific for APS than the aCL assay (about 99% and 90%, respectively, according to Helbert et al [47]), this is at the expense of significantly lower sensitivity for APS (about 75% and over 95%, respectively, in the same study). In other words, a proportion of APS patients will be negative for anti-β2GPI even though they may be positive for aCL.…”

Section: Limitations Of the Aps Classification Criteriamentioning

confidence: 99%