Abstract
The threshold between low and medium antibody levels for anticardiolipin (aCL) and anti-β2 glycoprotein I antibodies (aβ2GPI) for the diagnosis of antiphospholipid syndrome (APS) remains a matter of discussion. Our goal was to create a protocol for determining the low/medium antibody cut-off for aCL antibody methods based on a clinical approach, and utilize it to establish the clinically-relevant low/medium threshold for QUANTA Flash aCL chemiluminescent immunoassay (CIA) results. The study included 288 samples from patients with primary APS (n = 70), secondary APS (n = 42), suspected APS (n = 36), systemic lupus erythematosus (SLE) without APS (n = 96) and other connective tissue diseases (n = 44). All samples were tested for IgG and IgM aCL antibodies with QUANTA Flash CIA, along with traditional enzyme-linked immunosorbent assays (ELISAs) (QUANTA Lite). The assay specific low/medium threshold for QUANTA Flash aCL IgG and IgM assays (i.e., the equivalent of 40 GPL and MPL units) was established as 95 and 31 chemiluminescent units (CU), respectively, based on clinical performance and comparison to QUANTA Lite ELISAs. Agreement between CIA and ELISA assay results improved substantially when the platform-specific low/medium antibody threshold was used, as compared to agreement obtained on results generated with the assay cutoff: Cohen’s kappa increased from 0.85 to 0.91 for IgG aCL, and from 0.59 to 0.75 for IgM aCL results. This study describes a clinical approach for establishing the low/medium antibody threshold for aPL antibody assays, and successfully employs it to define 95 and 31 CU, respectively, as the low/medium cut point for QUANTA Flash aCL IgG and IgM results. This study can serve as a model for labs wishing to establish the appropriate low/medium aPL antibody threshold when implementing new aPL antibody assays.
Highlights
The updated classification criteria for definite antiphospholipid syndrome (APS), known as Hughes syndrome, specifies anticardiolipin and anti-β2 -glycoprotein I (β2 GPI) antibodies of IgG and/or IgM isotype in medium or high titer as one of the laboratory criteria [1]
Agreement between chemiluminescent immunoassays (CIA) and enzyme-linked immunosorbent assays (ELISAs) assay results improved substantially when the platform-specific low/medium antibody threshold was used, as compared to agreement obtained on results generated with the assay cutoff: Cohen’s kappa increased from 0.85 to 0.91 for IgG aCL, and from 0.59 to 0.75 for
This study describes a clinical approach for establishing the low/medium antibody threshold for aPL antibody assays, and successfully employs it to define 95 and 31 chemiluminescent units (CU), respectively, as the low/medium cut point for QUANTA Flash aCL IgG and IgM results
Summary
The updated classification criteria for definite antiphospholipid syndrome (APS), known as Hughes syndrome, specifies anticardiolipin (aCL) and anti-β2 -glycoprotein I (β2 GPI) antibodies of IgG and/or IgM isotype in medium or high titer as one of the laboratory criteria [1]. In the absence of a reference method, and in the light of the analytical diversity of aPL antibody assays, the use of the same unit type (GPL and MPL) by itself is not sufficient to achieve harmonization between antiphospholipid (aPL) antibody assays. This is evident by the different cut-off values of different brands of kits, and the wide range of results reported by labs during proficiency testing surveys [2,3,4,5]. Using the same low/medium threshold for all assays is unlikely to be an optimal to approach to achieve consistent and appropriate patient management
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