A review of 10 years of data from an external quality assurance program for antiphospholipid antibodies: no evidence for improved aCL and β2GPI assay standardization

Louise A. Wienholt, Alexander Richardson, Richard C. Wong, Kristie Chapman, Frederick J. Lee


Background: Anticardiolipin (aCL) and anti-β2-glycoprotein I (aβ2GPI) antibodies are important markers in the diagnosis of the antiphospholipid syndrome. Previous studies have shown significant variability in results obtained from different kits and manufacturers for these antibodies. In response to this lack of homogeneity, there have been international initiatives aimed at improving the reproducibility and standardization of these assays. To assess if these standardization initiatives have led to improved consistency in routine diagnostic laboratory reporting of these antibodies, we retrospectively reviewed 10 years of data from an External Quality Assurance (EQA) program.
Methods: Data submitted by laboratories participating in the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) antiphospholipid EQA program over a ten-year period (2009–2018) for IgG and IgM aCL and IgG aβ2GPI antibodies were reviewed. Changes in assay methodologies, consensus of results against the target set by RCPAQAP, and the number of laboratories reporting semi-quantitative results were assessed.
Results: Methodologies used for the detection of aCL and aβ2GPI antibodies have changed considerably since 2009, with a steady trend towards non-ELISA based methodologies, such as chemiluminescence, fluorescence immunoassay and Luminex based techniques. Consensus in resulting (defined as ≥80% concordance in reporting “negative” or “positive” results for a sample) did not significantly change across the 10-year period for any test. There was a significant decrease in the proportion of laboratories reporting semi-qualitative results (i.e., low/medium/high positive) for IgG aCL (P=0.0036) and IgG aβ2GPI antibodies (P=0.007). No significant change was noted for IgM aCL antibodies (P>0.999).
Conclusions: Despite concerted efforts by a number of international groups to improve the standardization of aCL and aβ2GPI antibodies assays, a review of data obtained over a 10-year period of EQA testing in diagnostic laboratories demonstrated that there is no evidence to support that these efforts have translated into improvements in the consistency of IgG/IgM aCL and IgG aβ2GPI antibody results.