Towards harmonized interpretation of anticardiolipin and anti-β2-glycoprotein I antibody detection for diagnosis of antiphospholipid syndrome using defined level intervals and likelihood ratios: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies.

BACKGROUND: Improving harmonization of the clinical interpretation of anticardiolipin (aCL) and anti-β2-glycoprotein I antibodies (aβ2GPI) IgG/IgM in the diagnosis of antiphospholipid syndrome (APS) is desirable. Likelihood ratios (LR) with corresponding test-result intervals can identify the power of a test to discriminate between a diseased and non-diseased patient and may be useful for the semiquantitative interpretation of aCL/aβ2GPI results.

OBJECTIVES: To determine moderate and high thresholds for aCL and aβ2GPI IgG/IgM determined with chemiluminescent immunoassay, enzyme-linked immunosorbent assay, fluorescence enzyme immunoassay, and multiplex flow immunoassay.

PATIENTS/METHODS: aCL and aβ2GPI IgG/IgM were determined with four solid-phase systems in a case-control study population including 381 APS patients and 727 controls. Interval-specific LR (IS-LR) were determined for ranges determined by prespecified specificity and sensitivity levels. Three methods were used for determining thresholds that separated low, moderate, and high positive antibody levels. Inter-assay agreement was checked with Cohen's kappa statistics.

RESULTS: Assay- and antibody-specific thresholds demonstrated increasing IS-LR, reflecting different clinical significance for low, moderate, and high levels, especially for IgG aCL and aβ2GPI and in thrombotic APS. IS-LR per antibody and unit range were comparable across solid-phase platforms resulting in enhanced harmonization of result interpretation. Agreement between assays for identifying high levels improved by semiquantitative interpretation compared to quantitative reporting.

CONCLUSIONS: aCL and aβ2GPI IgG/IgM moderate and high thresholds were determined for four analytical platforms. Thresholds improve harmonized interpretation of aCL/aβ2GPI levels across platforms. The proposed thresholds should be verified in an independent case-control study to check interlaboratory transferability.