IgG antibodies that recognize epitope Gly40-Arg43 in domain I of β2–glycoprotein I cause LAC, and their presence correlates strongly with thrombosis

Laat, Bas de; Derksen, R. H. W. M.; Urbanus, Rolf T.; Groot, Philip G. de

doi:10.1182/blood-2004-09-3387

Cited by 370 publications

(373 citation statements)

References 28 publications

(30 reference statements)

Supporting

Mentioning

347

Contrasting

Unclassified

Order By: Relevance

“…The bulk of the evidence favors aPL binding immunodominant epitopes located within the N-terminal (domain I) (13)(14)(15). The ability of anti-␤ 2 GPI antibodies purified from patients with autoimmune disease to bind domain I of ␤ 2 GPI has been shown to be strongly correlated with the occurrence of thrombosis in those patients (16). Studies on expressed mutants of whole ␤ 2 GPI with incorporated single-point substitution mutations within domain I identified the residues G40 and R43 as being important in conferring binding to aPL (14,17).…”

mentioning

confidence: 99%

“…Studies on expressed mutants of whole ␤ 2 GPI with incorporated single-point substitution mutations within domain I identified the residues G40 and R43 as being important in conferring binding to aPL (14,17). De Laat et al (16) identified a population of anti-␤ 2 GPI antibodies derived from patients with thrombosis that bind domain I exclusively. This binding was considerably reduced by the introduction of mutations G40E and R43G.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Binding of antiphospholipid antibodies to discontinuous epitopes on domain I of human β₂‐glycoprotein I: Mutation studies including residues R39 to R43

Ioannou¹,

Pericleous²,

Giles³

et al. 2007

Arthritis & Rheumatism

128

138

View full text Add to dashboard Cite

Objective. Pathogenic antiphospholipid antibodies (aPL) bind the self antigen N-terminal domain (domain I) of ␤ 2 -glycoprotein I (␤ 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.Methods. We 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.Results. E 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.Conclusion. The binding of aPL to ␤ 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.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Binding of antiphospholipid antibodies to discontinuous epitopes on domain I of human β₂‐glycoprotein I: Mutation studies including residues R39 to R43

Ioannou¹,

Pericleous²,

Giles³

et al. 2007

Arthritis & Rheumatism

128

138

View full text Add to dashboard Cite

show abstract

“…Isolated LAC was not a risk factor for deep vein thrombosis in the Leiden thrombophilia study [17]. Further, it was shown that antibodies directed against a specific epitope (Gly40-Arg43) in the domain I of b 2 GPI (anti domain I antibodies) are responsible for LAC activity as well as thrombosis [18]. The significance of b 2 GPI independent LAC activity or aCL antibodies is under scrutiny.…”

Section: Issues With the Current Diagnostic Criteria Of Aps And Propomentioning

confidence: 99%

The Laboratory Diagnosis of the Antiphospholipid Syndrome

Ahluwalia

Sreedharanunni

2016

Indian J Hematol Blood Transfus

View full text Add to dashboard Cite

The Antiphospholipid Syndrome (APS) is classified based on the presence of both clinical and laboratory criteria. Both sets of criteria are subject to much review and intense research as it is becoming increasingly clear that no single test is specific for defining this autoimmune disorder. A number of leading international bodies have released guidelines in an attempt to improve the laboratory testing and reporting. The current review is an appraisal of some of the literature pertaining to the laboratory testing.

show abstract

“…It has been repeatedly observed invitro prolongation coagulation test with positivity antibodies against DI [3,8].…”

Section: Journal Of Hematology and Thromboembolic Diseasesmentioning

confidence: 99%

“…Evidence of the pathogenicity of anti-DI antibodies comes from both in-vitro and in-vivo studies. First, anti-DI antibodies were repeatedly observed to induce in-vitro prolongation of clotting time [3][4][5][6][7][8].…”

Section: Journal Of Hematology and Thromboembolic Diseasesmentioning

confidence: 99%

Detection of Anti-Domain I β-2 Glycoprotein I Antibodies as New Potential Target in Antiphospholipid Syndrome Diagnosis

Slavík¹,

Janek²,

Úlehlová³

et al. 2017

J Hematol Thrombo Dis

View full text Add to dashboard Cite

Anti-cardiolipin antibodies (ACL) and anti-β-2-glycoprotein I antibodies (anti-2GPI) represent two out of three laboratory criteria for detection of antiphospholipid syndrome (APS). The domain I (DI) in anti-β-2-glycoprotein I is a new target for better identification of antibodies and may be associated with thrombotic risk in antiphospholipid syndrome.Anti-β2GPI antibodies specifically reacting with DI have a particular clinical importance being more commonly detected among patients with APS and other autoimmune diseases. This observation implies that compared with antibodies targeting the whole molecule, anti-DI antibodies have higher specificity for APS. Routine testing for anti-DI antibodies in clinical practice can be used for an easy differentiation of subjects carrying clinically meaningful anti-β2GPI antibodies from those individuals with a benign autoantibody profile.The aim of our study was to determine the significance of the domain I in the anti-β-2-glycoprotein I as a new biomarker for determining thrombotic risk in antiphospholipid syndrome.We investigate the DI anti-β2GPI on a group of 74 patients with antiphospholipid syndrome diagnosis. All patients have positive antibodies in at least one class ACL and anti-β2GPI antibodies.We detect DI anti-β2GPI positivity in 21 samples in our group. The thrombotic complications had been observed in 21 from 74 patients. The incidence of thrombotic complications in the total group was established as 28.4%, in comparison to the group DI anti-β2GPI positive with the incidence of thrombotic complications 57%. Performing of assay improved a positive predictive value from 25% pre-test to 68% for patients with positive test.The new chemiluminescent method for detection of DI anti-β2GPI shows a better compliance with clinical outcome than the actual diagnostic scheme.

show abstract

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

Cited by 370 publications

References 28 publications

Binding of antiphospholipid antibodies to discontinuous epitopes on domain I of human β₂‐glycoprotein I: Mutation studies including residues R39 to R43

Binding of antiphospholipid antibodies to discontinuous epitopes on domain I of human β₂‐glycoprotein I: Mutation studies including residues R39 to R43

The Laboratory Diagnosis of the Antiphospholipid Syndrome

Detection of Anti-Domain I β-2 Glycoprotein I Antibodies as New Potential Target in Antiphospholipid Syndrome Diagnosis

Contact Info

Product

Resources

About

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

Cited by 370 publications

References 28 publications

Binding of antiphospholipid antibodies to discontinuous epitopes on domain I of human β2‐glycoprotein I: Mutation studies including residues R39 to R43

Binding of antiphospholipid antibodies to discontinuous epitopes on domain I of human β2‐glycoprotein I: Mutation studies including residues R39 to R43

The Laboratory Diagnosis of the Antiphospholipid Syndrome

Detection of Anti-Domain I β-2 Glycoprotein I Antibodies as New Potential Target in Antiphospholipid Syndrome Diagnosis

Contact Info

Product

Resources

About

Binding of antiphospholipid antibodies to discontinuous epitopes on domain I of human β₂‐glycoprotein I: Mutation studies including residues R39 to R43

Binding of antiphospholipid antibodies to discontinuous epitopes on domain I of human β₂‐glycoprotein I: Mutation studies including residues R39 to R43