Detection of Anti-Cardiolipin and Anti-β2glycoprotein I Antibodies Differs between Platforms without Influence on Association with Clinical Symptoms

Chayouâ, Walid; Kelchtermans, Hilde; Moore, Gary; Gris, Jean‐Christophe; Musiał, Jacek; Wahl, Denis; Zuily, Stéphane; Gianniello, Francesca; Fontana, Pierre; Remijn, Jasper A.; Urbanus, Rolf T.; Laat, Bas de; Devreese, Katrien

doi:10.1055/s-0039-1679901

Cited by 39 publications

(68 citation statements)

References 31 publications

(60 reference statements)

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“…Automated systems limit the intralaboratory and interlaboratory variation for one system 36 . We have recently shown that with commercially available solid‐phase assays, even with eliminating interlaboratory and interoperator variation, there is still variable detection of aCL and aβ2GPI IgG/M between platforms 32 . In this study, a discrepancy of 36%, 60%, 53%, and 36% for aCL IgG, aCL IgM, aβ2GPI IgG, and aβ2GPI IgM positivity was observed, respectively.…”

Section: Anticardiolipin and Antibeta2‐glycoprotein I Antibodiesmentioning

confidence: 59%

“…aCL detection can confirm the positivity of aβ2GPI. Positivity of aCL without aβ2GP positivity should be interpreted with caution, since both parameters correlate well and discrepant results sometimes result from the use of assays from different manufacturers 12,32 …”

Section: Anticardiolipin and Antibeta2‐glycoprotein I Antibodiesmentioning

confidence: 99%

“…A major issue of concern remains the aCL and aβ2GPI interassay variation. External quality control programs and studies with human monoclonal antibodies illustrated that aCL and aβ2GPI IgG/M assays produce variable result 32‐34 . In general, ELISAs have shown large interlaboratory variation and limited consensus in external quality control programs 34,35 .…”

Section: Anticardiolipin and Antibeta2‐glycoprotein I Antibodiesmentioning

confidence: 99%

“…Detection of aCL IgG and aβ2GPI IgM resulted in the best agreement. However, still a substantial number of samples were in disagreement 32 . Discrepant samples displayed lower median aPL titers 32 .…”

Section: Anticardiolipin and Antibeta2‐glycoprotein I Antibodiesmentioning

confidence: 99%

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Testing for antiphospholipid antibodies: Advances and best practices

Devreese

2020

Int J Lab Hematology

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The diagnosis of antiphospholipid syndrome (APS) relies on the detection of circulating antiphospholipid antibodies (aPL). Currently, lupus anticoagulant (LAC), anticardiolipin (aCL), and antibeta2-glycoprotein I antibodies (aβ2GPI) IgG or IgM are included as laboratory criteria if persistently present. Progress has been made on the standardization of tests as guidelines on LAC testing and immunological assays for aCL and aβ2GPI are published. However, LAC measurement remains a complicated procedure with many pitfalls and interfered by anticoagulant therapy. Solid-phase assays for aCL and aβ2GPI still show interassay differences. These methodological issues make the laboratory diagnosis of APS challenging. In the interpretation of aPL results, antibody profiles help in identifying patients at risk. Noncriteria aPL, such as antibodies against the domain I of beta2-glycoprotein (aDI) and antiphosphatidylserine-prothrombin (aPS/PT) antibodies have been studied in the last years and may be useful in risk stratification of APS patients. But, aDI and aPS/PT are not included in the current diagnostic criteria and testing in daily practice is not recommended as these antibodies have no added value in the diagnosis of APS. This review will focus on the technical aspects of the laboratory methods, the clinical relevance of assays and interpretation of aPL results in the diagnosis of APS. K E Y W O R D S anticardiolipin antibodies, antiphospholipid syndrome, anti-β2 glycoprotein I antibodies, guidelines, lupus anticoagulant

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Section: Anticardiolipin and Antibeta2‐glycoprotein I Antibodiesmentioning

confidence: 59%

Section: Anticardiolipin and Antibeta2‐glycoprotein I Antibodiesmentioning

confidence: 99%

Section: Anticardiolipin and Antibeta2‐glycoprotein I Antibodiesmentioning

confidence: 99%

Section: Anticardiolipin and Antibeta2‐glycoprotein I Antibodiesmentioning

confidence: 99%

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Testing for antiphospholipid antibodies: Advances and best practices

Devreese

2020

Int J Lab Hematology

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“…Importantly, we hypothesized that the added value of the anti‐DI IgG assay measured by QUANTA Flash ® depends on the platform used to detect anti‐β2GPI and anti‐CL IgG. This hypothesis comes from our previously published results demonstrating a variable exposure of the G40‐R43 epitope on domain I of β2GPI coated in the different commercially available anti‐CL and anti‐β2GPI assays . In this multicenter study, we therefore determined the added value of anti‐DI testing to the current APS classification criteria, when anti‐CL and anti‐β2GPI were measured by four different commercially available assays.…”

Section: Discussionmentioning

confidence: 99%

Detection of anti‐domain I antibodies by chemiluminescence enables the identification of high‐risk antiphospholipid syndrome patients: A multicenter multiplatform study

Dai

Chayouâ

Kelchtermans

et al. 2020

Journal of Thrombosis and Haemostasis

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Background: Classification of the antiphospholipid syndrome (APS) relies predominantly on detecting antiphospholipid antibodies (aPLs). Antibodies against a domain I (DI) epitope of anti-β2glycoprotein I (β2GPI) proved to be pathogenic, but are not included in the current classification criteria. Objectives: Investigate the clinical value of detecting anti-DI IgG in APS.Patients/Methods: From eight European centers 1005 patients were enrolled. Anticardiolipin (CL) and anti-β2GPI were detected by four commercially available solid phase assays; anti-DI IgG by the QUANTA Flash ® β2GPI domain I assay.Results: Odds ratios (ORs) of anti-DI IgG for thrombosis and pregnancy morbidity proved to be higher than those of the conventional assays. Upon restriction to patients positive for anti-β2GPI IgG, anti-DI IgG positivity still resulted in significant ORs. When anti-DI IgG was added to the criteria aPLs or used as a substitute for anti-β2GPI IgG/anti-CL IgG, ORs for clinical symptoms hardly improved. Upon removing anti-DI positive patients, lupus anticoagulant remained significantly correlated with clinical complications. Anti-DI IgG are mainly present in high-risk triple positive patients, showing higher levels. Combined anti-DI and triple positivity confers a higher risk for clinical symptoms compared to only triple positivity.Conclusions: Detection of anti-DI IgG resulted in higher ORs for clinical manifestations than the current APS classification criteria. Regardless of the platform used to detect anti-β2GPI/anti-CL, addition of anti-DI IgG measured by QUANTA Flash ® did not improve the clinical associations, possibly due to reduced exposure of the pathogenic epitope of DI. Our results demonstrate that anti-DI IgG potentially helps in identifying high-risk patients.

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Bertin

Brodovitch

Beziane

et al. 2021

Arthritis & Rheumatology

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| 899 with ARDS (16%) without any specific aPL profile. Thus, it is difficult to draw conclusions based on so few aPL-positive patients. Because of the lack of a standardized assay and aPL heterogeneity, their detection is dependent on enzyme-linked immunosorbent assays (2), which were provided by different manufacturers in the 2 studies. In particular, coating or buffer composition can influence the interaction between cardiolipin and cofactor proteins (3), and can influence whether antibodies are detected or not. Moreover, knowing the difficulties of interpreting aPL positivity, we pay close attention to their routine detection. All positive samples are controlled in duplicate, and, to address the specificity, the absorbance of uncoated wells treated in the same conditions is subtracted in order to avoid nonspecific binding (4). In contrast to Frapard and colleagues who focused on patients in the ICU, we also included patients with severe COVID-19 who were not admitted to the ICU and observed that 29% were positive for IgG aCL (Figure 1A). There was no difference in IgG aCL levels between aCL-positive patients admitted versus those not admitted to the ICU (Figure 1B), suggesting that IgG aCL positivity in severe COVID-19 is not attributable to the pulmonary complications alone.If the link between viral infection and aPL detection is well described in the literature (5), the relationship between aPL positivity and lung injury is not obvious. To support their hypothesis, Frapard et al referenced a study by Wiedermann et al (6), in which an association between aPL positivity and lung injury was not shown except in 1 patient with catastrophic antiphospholipid syndrome (CAPS). In the literature, the association between aPL positivity and ARDS is rarely described and only reported in the context of APS or CAPS (7). Consistent with our results, Zuo et al ( 8) recently reported that half of patients hospitalized for

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Detection of Anti-Cardiolipin and Anti-β2glycoprotein I Antibodies Differs between Platforms without Influence on Association with Clinical Symptoms

Cited by 39 publications

References 31 publications

Testing for antiphospholipid antibodies: Advances and best practices

Testing for antiphospholipid antibodies: Advances and best practices

Detection of anti‐domain I antibodies by chemiluminescence enables the identification of high‐risk antiphospholipid syndrome patients: A multicenter multiplatform study

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