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Associations Among Antiphospholipid Antibody Types, Isotypes, and Titers: An AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Study

Gkrouzman, Elena; Willis, Rohan; Andrade, Danieli; Tektonidou, Maria G; Pengo, Vittorio; Ruiz-Irastorza, Guillermo; Belmont, H Michael; ... APS, ACTION; + view all (2023) Associations Among Antiphospholipid Antibody Types, Isotypes, and Titers: An AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Study. Laboratory Investigation , 103 (6) , Article 100147. 10.1016/j.labinv.2023.100147.

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Abstract

Several antiphospholipid antibody (aPL) profiles ("triple" and lupus anticoagulant [LA] positivity) are associated with a higher risk for clinical manifestations of antiphospholipid syndrome (APS). Further risk is correlated with higher levels of anticardiolipin (aCL) and anti-β2 glycoprotein-I antibodies (aβ2GPI), and with aPL persistence. Given that the three aPL tests detect partially overlapping sets of antibodies, the primary goal of this study was to characterize the associations among aPL tests using APS ACTION Core Laboratory data. The APS ACTION Registry includes annually followed adult patients with positive aPL based on the Revised Sapporo Classification Criteria. We analyzed baseline and prospective Core Laboratory data of the Registry for associations among aPL tests, using Spearman's rank correlation with Bonferroni adjusted significance level for multiple comparisons. An aPL Load was calculated based on six tests (aCL IgG/M/A and aβ2GPI IgG/M/A); a receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of the aPL Load in predicting LA positivity. In 351 patients simultaneously tested for LA, aCL, and aβ2GPI, the frequency of moderate-to-high (≥40 units) titers of aCL and aβ2GPI IgG/M/A was higher in patients who were positive for LA versus negative. An aPL Load was calculated for each patient to assess their overall aPL burden. For every one-point increase in aPL Load, the possibility of a positive LA test increased by 32% (OR 1.32, 95% CI 1.2, 1.5, p<.001). Based on Core Laboratory data from a large international registry, most aPL ELISA ≥40U and a high calculated aPL Load combining six aPL ELISAs were predictive of a positive LA. These data suggest that the combined quantitative burden of aPL may provide a mechanistic explanation of a positive LA.

Type: Article
Title: Associations Among Antiphospholipid Antibody Types, Isotypes, and Titers: An AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Study
Location: United States
DOI: 10.1016/j.labinv.2023.100147
Publisher version: https://doi.org/10.1016/j.labinv.2023.100147
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: antiphospholipid antibodies, antiphospholipid syndrome, lupus anticoagulant, anticardiolipin
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: https://discovery.ucl.ac.uk/id/eprint/10177846
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