التفاصيل البيبلوغرافية
| العنوان: |
Variability in Exposure of Epitope G40-R43 of Domain I in Commercial Anti-Beta2-Glycoprotein I IgG ELISAs. |
| المؤلفون: |
Pelkmans, Leonie, Kelchtermans, Hilde, de Groot, Philip G., Zuily, Stephane, Regnault, Veronique, Wahl, Denis, Pengo, Vittorio, de Laat, Bas |
| المصدر: |
PLoS ONE; Aug2013, Vol. 8 Issue 8, p1-9, 9p |
| مصطلحات موضوعية: |
EPITOPES, GLYCOPROTEINS, BLOOD coagulation disorders, ANTIPHOSPHOLIPID syndrome, IMMUNOGLOBULINS, GLYCINE |
| مستخلص: |
Background: A major problem for diagnosing the antiphospholipid syndrome (APS) is the high variability between commercial anti-β2glycoprotein I (β2GPI) assays. Predominantly antibodies reactive against cryptic epitope Glycine40-Arginine43 (G40-R43) in domain I are associated with an increased risk for thrombosis. Upon interaction with anionic surfaces β2GPI opens up, thereby exposing G40-R43. Objectives: To examine whether suboptimal exposure of epitope G40-R43 explains the variations in results observed between commercial assays. Methods: Two patient-derived monoclonal antibodies were tested on neutral versus anionic plates. Antibody P1-117 reacts with G40-R43 in the open conformation while P2-6 recognizes β2GPI irrespective of its conformation. These antibodies were tested in commercial anti-β2GPI assays (A–E). Results: In assay A, both antibodies showed equal reactivity towards β2GPI, indicating that all the β2GPI exposes G40-R43. In other assays P1-117 displayed lower reactivity than P2-6, demonstrating reduced G40-R43 availability. To exclude influences of other assay features, reactivity was re-examined on plates of assay A and B using the protocol/reagents from each assay. In all combinations, reactivity of both antibodies on a plate was comparable to results obtained with its own protocol/reagents, suggesting that the coating, rather than other assay components, accounts for the observed differences. In two patient cohorts we demonstrated that a number of domain I-reactive samples are missed in assays characterized by a decreased exposure of epitope G40-R43. Conclusions: Exposure of epitope G40-R43 on β2GPI is highly variable between commercial anti-β2GPI assays. As a consequence, patients can be falsely assigned negative in assays characterized by a reduced exposure of G40-R43. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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