B-093 Evaluation of the Association of Non-criteria Antiphospholipid Antibodies with the Presence of Lupus Anticoagulant
Authors: Saadalla A , Nandakumar V 
Published: September 2023

Abstract

Backrground
Laboratory diagnosis of the antiphospholipid antibody syndrome (APS) requires evidence ofpersistently positive lupus anticoagulant (LAC), detected using clot-based assays and/or thepresence of high-titer serum anti-cardiolipin (aCL) and/or anti-beta-2 glycoprotein-1 (aB2GPI)antibodies, measured by semi-quantitative solid-phase immunoassays. Several non-criteria anti-phospholipid antibodies (NC-APLA) have been proposed as candidates for APS diagnosis:phosphatidyl-serine/ prothrombin (aPS/PT; IgM and IgG isotypes), anti-phosphatidyl serine (aPS;IgM and IgG), anti-prothrombin (aPT-IgG). However, their diagnostic relevance in routine APSevaluation is still unclear. The objectives of this study were 1) to determine the prevalence andassociation of NC-APLA in relation to LAC, aCL and aB2GPI antibodies’ positivity,independently and in combination and, 2) to assess the ability of NC-APLA to predict LACactivity, as an indirect measure of their function.

Methods
Results from 492 patients submitted for antiphospholipid antibody (APLA) panel or standaloneserology testing between January 2016 to January 2023 were retrieved in accordance withinstitutional guidelines. Patients were grouped according to LAC status and serology positivity(using manufacturer-suggested cutoff) into three groups: Single-positives (SP) for LAC, aCL oraB2GPI; Double-positives (DP) for aCL and aB2GPI; Triple-positives (TP) for LAC, aCL andaB2GPI. NC-ALPA titers were compared between LAC-positive and negative patients. Statisticalsignificance was established using unpaired Student’s t-test. Receiver operating curve (ROC)analysis was employed to assess the ability of NC-APLA to predict LAC status.

Results
Out of the total 492 patients, 1.8% (9/492) were TP, 2.4% (12/492) were DP and 24.7% (122/492)were SP. All NC-APLA titers were significantly higher in TP than in SP patients (P &lt; 0.001).aPS/PT IgG (Mean: 76.3 vs 12.8 Units) and aPS IgG (Mean: 64.8 vs 5.5 GPS) antibodies weresignificantly higher in TP than DP patients (P = 0.008 and &lt;0.0001, respectively). aPS/PT IgM(Mean: 62.5 vs 19.4 Units) and aPS IgM titers (Mean 31.9 vs 7.7 MPS) were significantly higherin DP compared to SP patients (P &lt; 0.0001). When classified by LAC status, 40 patients werepositive and 452 were negative. Levels of all NC-APLA antibody titers (P &lt; 0.0001) followed byaCL (Mean IgG 21.9 vs 7.8 GPL; IgM 20 vs 12.6 MPL; P &lt; 0.01) and aB2GPI (Mean IgG 20.1 vs 4.9 SGU; IgM 13.8 vs 7.6 SMU, P &lt; 0.001) antibodies were significantly higher in LAC-positivepatients compared to the LAC-negative individuals. ROC analyses based on the LAC statusresulted in the highest area under the curve (AUC, 95% CI) for aPS/PT IgM (0.72, 0.62 to 0.81)Private Information and aPS/PT IgG (0.74, 0.65 to 0.83) antibodies relative to aCL (IgM:0.53, 0.43 to 0.64; IgG:0.66, 0.56 to 0.77) or aB2GPI (IgM:0.5, 0.51 to 0.72 and IgG:0.6, 0.51 to 0.72) antibodies; aPS IgMand aPT IgG displayed similar performances (0.65, 0.54 to 0.75 and 0.66, 0.57 to 0.74,respectively). Whereas aPS IgG was of lower AUC (0.58, 0.48 to 0.68).

Conclusion
Our data demonstrated that at high titers, NC-APLA, display increased association with LACpositivity in comparison to aCL or aB2GPI antibody levels. Particularly, aPS/PT antibodiesdisplayed the superior ability to determine the LAC presence.Private Information