IgG antibodies that recognize epitope Gly40-Arg43 in domain I of β2–glycoprotein I cause LAC, and their presence correlates strongly with thrombosis
Abstract
Anti-beta(2)-glycoprotein I antibodies are known to have a heterogeneous reactivity against beta(2)-glycoprotein I. We performed this study to characterize the epitope on beta(2)-glycoprotein I to which pathologic anti-beta(2)-glycoprotein I antibodies are directed. Plasma samples from 198 patients with various systemic autoimmune diseases were tested for the presence of lupus anticoagulant and anti-beta(2)-glycoprotein I immunoglobulin G (IgG) antibodies. The reactivity of the anti-beta(2)-glycoprotein I-positive samples was further tested by coating recombinant full-length beta(2)-glycoprotein I and 8 deletion mutants of beta(2)-glycoprotein I onto hydrophilic and hydrophobic enzyme-linked immunosorbent assay (ELISA) plates. Full-length beta(2)-glycoprotein I with point mutations in domain I at positions 8, 40, and 43 were used in inhibition experiments. Fifty-two patients with anti-beta(2)-glycoprotein I IgG antibodies could be divided into 2 patterns. Type A antibodies only recognize domain I when coated onto hydrophobic plates; they do not recognize domain I coated onto hydrophilic plates. Type B antibodies have heterogeneous reactivity for all domains. Type A antibodies recognize the epitope around amino acids Gly40-Arg43 and cause lupus anticoagulant activity. In contrast to type B antibodies, those of type A strongly correlated with thrombosis. In conclusion, antibodies directed at domain I (epitope comprising Gly40 and Arg43) have lupus anticoagulant activity and strongly associate with thrombosis.
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aCL ELISA positivity can arise from antibodies against cardiolipin-binding proteins.
“Indeed, the LA test is positive in the presence of ab2GPI and anti-prothrombin antibodies, the aCL ELISA is positive in the presence of antibodies directed against cardiolipin-binding proteins and the ab2GPI ELISA may identify antibodies that are distinct to those relevant to the syndrome [5].”
From Clinical course of high‐risk patients diagnosed with antiphospholipid syndrome (2010) · cites this paper as [5]
LA positivity can arise from ab2GPI and anti-prothrombin antibodies.
“Indeed, the LA test is positive in the presence of ab2GPI and anti-prothrombin antibodies, the aCL ELISA is positive in the presence of antibodies directed against cardiolipin-binding proteins and the ab2GPI ELISA may identify antibodies that are distinct to those relevant to the syndrome [5].”
From Clinical course of high‐risk patients diagnosed with antiphospholipid syndrome (2010) · cites this paper as [5]
ab2GPI ELISA may detect antibodies unrelated to the syndrome.
“Indeed, the LA test is positive in the presence of ab2GPI and anti-prothrombin antibodies, the aCL ELISA is positive in the presence of antibodies directed against cardiolipin-binding proteins and the ab2GPI ELISA may identify antibodies that are distinct to those relevant to the syndrome [5].”
From Clinical course of high‐risk patients diagnosed with antiphospholipid syndrome (2010) · cites this paper as [5]
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References 29 · Cited by 378
- Authors
- de Laat, B., Derksen, R. H. W. M., Urbanus, R. T., & de Groot, P. G.
- Affiliations
- From the Departments of Haematology and Rheumatology and Clinical Immunology, University Medical Centre, Utrecht, the Netherlands.
- University Medical Center Utrecht (NL)
- ORCID
- Urbanus, Rolf T.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2005-02-15
- Volume
- 105
- Issue
- 4
- Pages
- 1540-1545
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2143086319
- Cited by
- 378
- References
- 29
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 13 · 2023: 12 · 2022: 7 · 2021: 16 · 2020: 16 · 2019: 16 · 2018: 26 · 2017: 20 · 2016: 18 · 2015: 17 · 2014: 28 · 2013: 15 · 2012: 21
- FWCI
- 8.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Vasculitis and related conditions
- Keywords
- anti-beta2-glycoprotein I antibodies, beta2-glycoprotein I, lupus anticoagulant, thrombosis, epitope mapping, domain I, IgG, systemic autoimmune diseases
- MeSH terms
- Adult, Antibody Specificity, Epitopes, Arginine, Binding Sites, Antibody, Enzyme-Linked Immunosorbent Assay, Female, Glycine, Glycoproteins, Humans, Immunoglobulin G, Male, Thrombosis, Odds Ratio, Lupus Coagulation Inhibitor, Protein Structure, Tertiary, beta 2-Glycoprotein I
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