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Variability in Exposure of Epitope G40-R43 of Domain I in Commercial Anti-Beta2-Glycoprotein I IgG ELISAs.
- Source :
- PLoS ONE; Aug2013, Vol. 8 Issue 8, p1-9, 9p
- Publication Year :
- 2013
-
Abstract
- Background: A major problem for diagnosing the antiphospholipid syndrome (APS) is the high variability between commercial anti-β<subscript>2</subscript>glycoprotein I (β<subscript>2</subscript>GPI) 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 β<subscript>2</subscript>GPI 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 β<subscript>2</subscript>GPI irrespective of its conformation. These antibodies were tested in commercial anti-β<subscript>2</subscript>GPI assays (A–E). Results: In assay A, both antibodies showed equal reactivity towards β<subscript>2</subscript>GPI, indicating that all the β<subscript>2</subscript>GPI 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 β<subscript>2</subscript>GPI is highly variable between commercial anti-β<subscript>2</subscript>GPI assays. As a consequence, patients can be falsely assigned negative in assays characterized by a reduced exposure of G40-R43. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 8
- Issue :
- 8
- Database :
- Complementary Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 90071426
- Full Text :
- https://doi.org/10.1371/journal.pone.0071402