“New” Antigenic Targets and Methodological Approaches for Refining Laboratory Diagnosis of Antiphospholipid Syndrome

Abstract

Antiphospholipid antibodies (aPLs) are a heterogeneous group of antibodies directed against phospholipids or protein/phospholipid complexes. Currently, aPLs are assessed using either “solid-phase” assays that identify anticardiolipin antibodies and anti-β2-glycoprotein I antibodies or “liquid-phase” assay that identifies lupus anticoagulant. However, in the last few years, “new” antigenic targets and methodological approaches have been employed for refining laboratory diagnosis of antiphospholipid syndrome (APS). In this review the potential diagnostic value of antibodies to domains of β2-GPI, prothrombin/phosphatidylserine, vimentin/cardiolipin, protein S, protein C, annexin A2, annexin A5, and phospholipid antigens is discussed. Moreover, new technical approaches, including chemiluminescence, multiline dot assay, and thin layer chromatography (TLC) immunostaining, which utilize different supports for detection of aPL, have been developed. A special focus has been dedicated on “seronegative” APS, that is, those patients with a clinical profile suggestive of APS (thromboses, recurrent miscarriages, or foetal loss), who are persistently negative for the routinely used aPL. Recent findings suggest that, in sera from patients with SN-APS, antibodies may be detected using “new” antigenic targets (mainly vimentin/cardiolipin) or methodological approaches different from traditional techniques (TLC immunostaining). Thus, APS represents a mosaic, in which antibodies against different antigenic targets may be detected thanks to the continuously evolving new technologies.

Detection of multiple annexin autoantibodies in a patient with recurrent miscarriages, fulminant stroke and seronegative antiphospholipid syndrome

“…Recently, autoantibodies against AnxA5 were found to be present in up to 17% of obstetric manifestations of APS cases, being the only serologic parameter significantly associated with miscarriage ( 19 ). However, due to inconsistent results among studies ( 8 ) the clinical correlation of autoantibodies against AnxA5 is still controversial discussed. Here, we detected moderate reactivity of IgM isotype antibodies against AnxA5, but we found considerably high reactivity of IgM isotype autoantibodies against AnxA2 and AnxA8 in the serum of our seronegative APS patient that suffered six miscarriages.…”

“…The lupus anticoagulant test is the most predictive value for venous and arterial thrombosis in patients with suspected APS ( 7 ), whereas a high intermethod variability for aCL assays exists. This explains the low utility of aCL testing ( 8 ). The diagnostic value of the major epitope of ß2GPI is still controversial discussed due to potential conformational changes during the immunoassay which may lead to epitope masking effects.…”

Anti-phospholipid Antibodies and Smoking: An Overview

“…Over the past two decades, other lipids and other cofactors Fig. 1 The role of antiphospholipid antibodies and possible Bsecond hits^in the generation of thrombosis Clinic Rev Allerg Immunol have been identified and evaluated in APS patients [28,29]. In a recent meta-analysis [30], Reynaud et al reported that LA and aCL were significantly associated with venous thrombosis; in addition to these two biomarkers, there were significant associations between arterial thrombosis and the following antibodies, β2GPI, anti-prothrombin (aPT-the antibody that is likely responsible for positive lupus anticoagulant results), and anti-phosphatidylserine (aPS).…”

Structural and lipid-binding characterization of human annexin A13a reveals strong differences with its long A13b isoform

“…annexins A2, A4 and several others) ( Mussunoor and Murray, 2008;Wang and Lin, 2014;Wei et al, 2015), resistance to chemotherapy [annexin A13 (AnxA13)] (Reiske et al, 2010) to inflammation and autoimmunity (i.e. annexin A1, A2 or A5) (D'Acquisto et al, 2013;Misasi et al, 2015).…”