Multicenter study to improve clinical interpretation of anticardiolipin and anti-beta2-glycoprotein I antibody test results for diagnosis of antiphospholipid syndrome.

Background: Anti-cardiolipin (aCL) and anti-beta2-glycoprotein I (aβ2GPI) antibodies are laboratory markers important for antiphospholipid syndrome (APS) diagnosis and classification. There is an important inter-assay variation among aCL and aβ2GPI assays. This study aims to harmonize aCL and aβ2GPI test result interpretation across assays.

Methods: Commercial aCL IgG/M and aβ2GPI IgG/M assays of three different diagnostic companies (Thermo Fisher Scientific, Orgentec, Werfen) were evaluated using 176 diagnostic samples from patients with APS and 433 disease controls. International APS reference materials (Harris/Louisville, Koike/Sapporo, NIBSC 21/266) were analysed to evaluate traceability. Reference values were verified using 120 healthy controls.

Results: Using manufacturer's proposed cut-offs, there was large variability in diagnostic sensitivity and specificity among assays. Thresholds corresponding to 97.5% and 99.5% specificity in diseased controls were used to delimit test result intervals [negative (<97.5% specificity threshold), weak positive and high positive (>99.5% specificity threshold)]. Test result interval-specific likelihood ratios (LRs) were concordant across the different aCL and aβ2GPI assays. For all assays, the LR for APS increased with increasing antibody level. Higher LRs were found for IgG than for IgM assays and for double and triple antibody positivity. The added diagnostic value of aβ2GPI IgM was limited.

Conclusions: Defining thresholds for antibody levels and assigning test result interval-specific LRs allows alignment of clinical interpretation for aCL and aβ2GPI assays.