Identification of high thrombotic risk triple‐positive antiphospholipid syndrome patients is dependent on anti‐cardiolipin and anti‐β2glycoprotein I antibody detection assays

Abstract

Background The antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity with the persistent presence of antiphospholipid antibodies (aPL). Triple-positivity (i.e. positivity for lupus anticoagulant [LAC], anti-cardiolipin [aCL] and anti-β2glycoprotein I [aβ2GPI] antibodies) is associated with a high thrombotic risk. Objectives We investigated the variability in triple-positivity detection by measuring the same samples with four commercially available solid phase assays. In addition, the added clinical value of aPL in LAC-positive patients was investigated, as well as the association of IgM triple-positivity and thrombosis. Patients/Methods We included 851 patients from seven European medical centers. Anti-CL and aβ2GPI IgG/IgM antibodies were determined by four platforms: BioPlex 2200, ImmunoCap EliA, ACL AcuStar and QUANTA Lite ELISA . Results Triple-positivity detection by solid phase assays varied, ranging from 89 up to 118 in thrombotic APS patients (n = 258), of which 86 were detected independent of the platform. Lupus anticoagulant positivity resulted in an odds ratio (OR) for thrombosis of 3.4; triple-positivity (irrespective of the isotype) increased the OR from 4.3 up to 5.2, dependent on the platform. Triple-positivity solely for the IgM isotype did not increase the OR for thrombosis compared with LAC positivity. The highest OR for thrombosis was reached for positivity for IgG and IgM aβ2GPI and aCL (8.6 up to 28.9). Conclusions Triple-positivity proved to be highly associated with thrombosis, but identification is assay dependent. Within triple-positivity, IgM antibodies only have an added clinical value in patients positive for IgG antibodies.

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

“…Clinical studies confirm that triple positivity in APS patients and asymptomatic aPL carriers indicates a high risk of recurrence of thrombosis or development of a first thrombotic event, respectively . Although identification of triple positives is dependent on the solid‐phase assay used, the percentage of anti‐DI IgG positives in individuals with distinct antibody profiles were comparable for the four tested solid‐phase assays. In this study, a very good agreement was found between triple positivity and anti‐DI IgG positivity, irrespective of the solid‐phase assay used (Table S5), which is consistent with previous studies .…”

Antiphospholipid antibodies in patients with COVID‐19: A relevant observation?

“…In this COVID‐19 cohort, the role of IgA is unclear, without added value on top of the current classification criteria, equally as previously illustrated in APS 10,21,30 …”

Challenges and Advances in SLE Autoantibody Detection and Interpretation

“…Recent reports indicate the value of this assay in risk management [135] and predicting thrombosis and late pregnancy morbidity [137]. However, as a word of caution, there is variation of results in different commercially available assays [138].…”

“…Although the presence of anti-PS/PT antibodies appear to be independent of the LA, they may be a potential substitute for the troubled LA assay [146,147]. The clinical utility of these assays, however, is limited by a paucity of prospective clinical data and lack of standardization [138]. Therefore, additional studies are required before any "noncriteria" immunoassays are included in standard APS classification criteria.…”