Antiphospholipid Syndromes with Anti-Human β2-Glycoprotein I Antibodies despite Negative Reactivity in Conventional aPL and LA Assays

Guérin, V.; Couchouron, Anne; Vergnes, C.; Parrens, E.; Vernhes, J P; Constans, J.; Boisseau, M. R.

doi:10.1055/s-0038-1656102

Cited by 8 publications

(3 citation statements)

References 4 publications

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“…Modified criteria including LA positivity as equivalent to a high aCL titer have been generally used, but the original data has not been republished with this inclusion. It is well established, however, that patients with primary or secondary APS may have a negative aCL result but may be positive for LA or occasionally anti-B2GPI in isolation (39), sometimes even with a nontreated polystyrene ELISA plate (17).…”

Section: Sensitivity and Specificity Of Aplmentioning

confidence: 99%

Testing for and Clinical Significance of Anticardiolipin Antibodies

Reddel

Krilis

1999

Clin Diagn Lab Immunol

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The disputed nomenclature of the antibodies associated with the antiphospholipid syndrome (APS) can easily confuse the reader. In this paper we use the historical terms; thus, "antiphospholipid antibodies" (aPL) refers to antibodies associated with the clinical syndrome of venous and arterial thrombosis, recurrent fetal loss, livido reticularis, thrombocytopenia, and other, less common manifestations, termed APS. This syndrome may be primary or secondary in association with other autoimmune conditions such as systemic lupus erythaematosus (SLE). aPL can be divided into the lupus anticoagulants (LA), detected by in vitro clotting tests, and antibodies detected by solid-phase enzyme-linked immunosorbent assays (ELISA), which include anticardiolipin antibodies (aCL). This review covers the solid-phase assays for aPL, but not the LA tests usually performed in a hematology laboratory. These terms are used to maintain historical and keyword search consistency. Clinically significant aCL detected in the aCL ELISA and also in some cases of LA are in fact largely directed to a plasma protein, ␤ 2-glycoprotein I (B2GPI) (48, 50, 62), with the B2GPI itself binding to phospholipid in the assay. True aPL, although detected in the aCL ELISA, are false positive and are usually not associated with the APS. In addition, cardiolipin may not necessarily be the best phospholipid for detecting aCL, and phosphatidylserine, phosphatidylethanolamine, and phospholipid mixtures have also been used; some of these may also detect different antibodies (82, 86). The reader will see the terms "antiphospholipid/cofactors syndrome," "antiphospholipid-protein syndrome," and "Hughes' syndrome" used elsewhere referring to APS; no doubt, further terms will be introduced when the physiologic mechanism of the antibodies becomes clear.

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Section: Sensitivity and Specificity Of Aplmentioning

confidence: 99%

Testing for and Clinical Significance of Anticardiolipin Antibodies

Reddel

Krilis

1999

Clin Diagn Lab Immunol

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“…Anti-␤ 2 -GPI antibodies were shown to be more specific for thrombosis than conventional aCL [15][16][17] and can occasionally be the only positive assay associated with the aPS. 18,19 ELISA kits for antibodies against ␤ 2 -GPI are currently available and FDA approved.…”

Section: See Related Article Page 1759mentioning

confidence: 99%

Antiphospholipid-Protein Antibodies and Ischemic Stroke

Tanné

Triplett

Levine

1998

Stroke

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“…Conversely, APAs measured with specific immunoassays are mainly targeted at epitopes only exposed when complexes of ß2GPI and anionic PLP are coated on a solid surface [23,27]. These antibodies are very heterogeneous, and some of them can also bind to insolubilized ß2GPI alone [25,26,[36][37][38][39][40][41], and in very rare cases, to insolubilized ß2GPI alone but not to its PLP complexes [42][43][44]. The clinical significance of these antibody specificities and their isotypes is still discussed and under evaluation [26,[45][46][47][48].…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Approach of Phospholipid-Dependent Antibodies

Amiral¹

1999

Pathophysiol Haemos Thromb

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Recent scientific developments enable to better understand the strong heterogeneity of assay methods for phospholipid (PLP)-dependent antibodies, measured as lupus anticoagulant (LA) or as anti-PLP antibodies (APA). These latter are actually targeted at complexes of β₂-glycoprotein I (β2GPI) and anionic PLP and also react with insolubilized β2GPI alone in some patients. Although APA present little species specificity for β2GPI, some of them bind preferentially to complexes of human β2GPI and PLP. LAs are diagnosed with screening assays (dPT, dRVVT, KCT, APTT); their sensitivity is dependent on the concentration and type of PLPs used. They are either β2GPI or prothrombin dependent. Based on the antibody-neutralizing capacity of PLP preparations (such as hexagonal phase phosphatidylethanolamine) or their bypassing activity, confirmatory assays enable to confirm LA. LAs and APAs bind to different epitopes on β2GPI or its complexes with PLP. Major characteristics of APA assays are: the capture antigen (PLPs, β2GPI source); its optimization and density on micro-ELISA plates; the efficacy of postcoating saturation; the animal serum used for saturation and diluent; the second antibody which must avoid nonspecific interactions; the calibrators proposed and their reference to international standards; the cutoff between the normal and the pathological ranges; the assay sensitivity and overall specificity for APAs. New optimized assays have been developed to meet these criteria. They are designed with PLP-coated plates, saturated first with immunoglobulin-free human serum as a source of β2GPI, then with goat serum also used in diluent. The cutoff value is determined with at least 200 normal plasma samples (mean + 3 standard deviations or 99th percentiles) and plasma samples from patients without APAs. This approach offers both optimized specificity and sensitivity for testing APAs, along with a good standardization and it helps to measure the true APAs associated with pathology.

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Antiphospholipid Syndromes with Anti-Human β2-Glycoprotein I Antibodies despite Negative Reactivity in Conventional aPL and LA Assays

Cited by 8 publications

References 4 publications

Testing for and Clinical Significance of Anticardiolipin Antibodies

Testing for and Clinical Significance of Anticardiolipin Antibodies

Antiphospholipid-Protein Antibodies and Ischemic Stroke

Diagnostic Approach of Phospholipid-Dependent Antibodies

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