ArticleArthritis and rheumatism2007
Binding of antiphospholipid antibodies to discontinuous epitopes on domain I of human beta(2)-glycoprotein I: mutation studies including residues R39 to R43.
Article in Arthritis and rheumatism, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 131 citations in OpenAlex.
- A Common Missense Variant, W335S, in β2-Glycoprotein I (APOH) is Associated with Increased Autoantibody Levels but Reduced Venous Thromboembolism Risk.medRxiv : the preprint server for health sciences · 2026Article
- Article
- The J-shape of β2GPI reveals a cryptic discontinuous epitope across domains I and II.Journal of structural biology: X · 2025Article
- Understanding the structure of βBlood vessels, thrombosis & hemostasis · 2025Review
- Article
- Identification of thrombosis-related conformational binding epitopes on domain I of β2-glycoprotein I.Thrombosis research · 2024Article
- Article
- Epitope of antiphospholipid antibodies retrieved from peptide microarray based on R39-R43 of β2-glycoprotein I.Research and practice in thrombosis and haemostasis · 2022Article
- PEGylated Domain I of Beta-2-Glycoprotein I Inhibits Thrombosis in a Chronic Mouse Model of the Antiphospholipid Syndrome.Frontiers in immunology · 2022Article
- Cardiolipin interacts with beta-2-glycoprotein I and forms an open conformation-Mechanisms analyzed using hydrogen/deuterium exchange.Protein science : a publication of the Protein Society · 2021Article
- Beta2 glycoprotein I-derived therapeutic peptides induce sFlt-1 secretion to reduce melanoma vascularity and growth.Cancer letters · 2020Article
- Review
- Anti-beta-2-glycoprotein I domain 1 identifies antiphospholipid antibodies-related injuries in patients with concomitant lupus nephritis.Journal of nephrology · 2020Article
- The role of beta-2-glycoprotein I in health and disease associating structure with function: More than just APS.Blood reviews · 2020Review
- Pathogenic Autoreactive T and B Cells Cross-React with Mimotopes Expressed by a Common Human Gut Commensal to Trigger Autoimmunity.Cell host & microbe · 2019Article
- New insight into antiphospholipid syndrome: antibodies to β2glycoprotein I-domain 5 fail to induce thrombi in rats.Haematologica · 2019Article
- Environmental Triggers of Autoreactive Responses: Induction of Antiphospholipid Antibody Formation.Frontiers in immunology · 2019Review
- The IgA Isotype of Anti-β2 Glycoprotein I Antibodies Recognizes Epitopes in Domains 3, 4, and 5 That Are Located in a Lateral Zone of the Molecule (L-Shaped).Frontiers in immunology · 2019Article
- Update on Antiphospholipid Syndrome: Ten Topics in 2017.Current rheumatology reports · 2018Review
- Antiphospholipid Antibodies to Domain I of Beta-2-Glycoprotein I Show Different Subclass Predominance in Comparison to Antibodies to Whole Beta-2-glycoprotein I.Frontiers in immunology · 2018Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
objectivePathogenic antiphospholipid antibodies (aPL) bind the self antigen N-terminal domain (domain I) of beta(2)-glycoprotein I (beta(2)GPI), with residues G40-R43 being important. However, peptides homologous to other regions of domain I have also been shown to bind aPL. Furthermore, there are no published reports of the effects of altering R39, which has greater surface exposure than the G40-R43 residues.
methodsWe used a novel, efficient method of production and purification of human domain I by Escherichia coli to create multiple mutants of domain I. These domain I mutants were then screened for binding to a range of polyclonal IgG purified from patients with antiphospholipid syndrome, using both solid-phase and fluid-phase assays.
resultsE coli-expressed purified domain I selectively bound IgG derived from patients with antiphospholipid syndrome. In region R39-R43, the R39S mutation had the greatest effect in terms of reducing binding to a panel of aPL in the fluid phase (mean +/- SD inhibition 14 +/- 18.5% versus 44.1 +/- 31.7% for G40E and 62.9 +/- 25.7% for wild-type domain I). Conversely, altering both D8 and D9 to S8 and G9, respectively, had the effect of enhancing binding to aPL in the fluid phase. Adding the remainder of the domain I-II interlinker resulted in enhanced binding over wild-type in the solid phase but not the fluid phase.
conclusionThe binding of aPL to beta(2)GPI domain I is complex and likely to involve discontinuous epitopes that include R39 in addition to G40-R43, the domain I-II interlinker, and possibly D8 and D9. Domain I variants with enhanced binding to aPL compared with wild-type domain I may aid in the development of novel therapies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.