Multicenter study to improve clinical interpretation of anticardiolipin and anti-β2-glycoprotein I antibody test results for diagnosis of antiphospholipid syndrome.

Background: Anticardiolipin (aCL) and anti-β2-glycoprotein I (aβGPI) antibodies are laboratory markers important for antiphospholipid syndrome (APS) diagnosis and classification. There is an important interassay variation among aCL and aβGPI assays.

Objectives: This study aimed to harmonize aCL and aβGPI test result interpretation across assays.

Methods: Commercial aCL immunoglobulin (Ig) G/IgM and aβGPI IgG/IgM assays from 3 different diagnostic companies (Thermo Fisher Scientific, Orgentec, and Werfen) were evaluated using 176 diagnostic samples from patients with APS and 433 diseased controls. International APS reference materials (Harris/Louisville, Koike/Sapporo, National Institute of Biological Standards and Controls 21/266) were analyzed to evaluate traceability. Reference values were verified using samples from 120 healthy controls.

Results: Using the manufacturers' proposed cutoffs, 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 aβGPI 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 aβGPI IgM was limited.

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