Antiphospholipid Antibody Assays in 2021: Looking for a Predictive Value in Addition to a Diagnostic One

Abstract

Antiphospholipid antibodies (aPL) are mandatory for the diagnosis but are also a risk factor for the antiphospholipid syndrome (APS) clinical manifestations. Lupus anticoagulant (LA), anticardiolipin (aCL), and anti-beta2 glycoprotein I (β2GPI) assays are the formal laboratory classification/diagnostic criteria. Additional nonclassification assays have been suggested; among them, antiphosphatidylserine-prothrombin (aPS/PT) and antidomain 1 β2GPI antibodies are the most promising ones although not yet formally accepted. aPL represent the example of a laboratory test that moved from dichotomous to quantitative results consistent with the idea that reporting quantitative data offers more diagnostic/prognostic information for both vascular and obstetric manifestations. Although the general rule is that the higher the aPL titer, the higher the test likelihood ratio, there is growing evidence that this is not the case for persistent low titers and obstetric events. LA displays the highest diagnostic/prognostic power, although some isolated LAs are apparently not associated with APS manifestations. Moreover, isotype characterization is also critical since IgG aPL are more diagnostic/prognostic than IgA or IgM. aPL are directed against two main autoantigens: β2GPI and PT. However, anti-β2GPI antibodies are more associated with the APS clinical spectrum. In addition, there is evidence that anti-β2GPI domain 1 antibodies display a stronger diagnostic/prognostic value. This finding supports the view that antigen and even epitope characterization represents a further step for improving the assay value. The strategy to improve aPL laboratory characterization is a lesson that can be translated to other autoantibody assays in order to improve our diagnostic and prognostic power.

Added value of antiphosphatidylserine/prothrombin antibodies in the workup of thrombotic antiphospholipid syndrome: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies

“…Seronegative APS is considered in patients clinically suggestive for APS without presence of any laboratory criterion 33 . Lack of evidence feeds the debate on non‐criteria aPL such as IgA aCL/aβ2GPI, anti‐domain I β2GPI, and aPS/PT 11,12 . This study evaluated whether aPS/PT IgG/IgM has added value to current laboratory criteria for APS diagnosis or whether it could replace LAC in current laboratory criteria.…”

Anti-Phospholipid Antibodies and Coronavirus Disease 2019: Vaccination Does Not Trigger Early Autoantibody Production in Healthcare Workers

“…The positive results were found at low titer with weak clinical diagnostic/prognostic value. This was particularly true for IgA anti-b2GPI positivity (25,26).…”

Pathogenesis of the obstetric antiphospholipid syndrome: the key role of beta 2 glycoprotein I

“…There is a general agreement that antiphospholipid antibodies (aPL) do not bind directly to anionic PLs but a complex between PL and PL-binding proteins. β2GPI was identified as the most relevant co-factor for aPL [5,6]. β2GPI-dependent antibodies bind the target antigen: i) when complexed with cardiolipin (CL)-coated plates (i.e.…”