A comparative study of anti-ADAMTS13 antibody dynamics in immune-mediated Thrombotic Thrombocytopenic Purpura

Abstract

BackgroundThrombotic Thrombocytopenic Purpura, particularly its immune-mediated variant (iTTP), necessitates accurate diagnostic approaches for effective management. ObjectiveTo compare a chemiluminescence immunoassay (CLIA) and an enzyme-linked immunosorbent assay (ELISA) for testing ADAMTS13 activity and detecting anti-ADAMTS13 antibody (AAb) in patients with iTTP. MethodsThis study involved 31 paired samples from 12 iTTP patients. ADAMTS13 activity was measured using the HemosIL AcuStar (IL) (CLIA) and Technozym (Technoclone) activity assay (ELISA). The presence of AAb was assessed using Technozym ADAMTS13-INH assay (ELISA) and HemosIL Acustar activity (CLIA) within a Bethesda assay, following mixing with normal pool plasma. VWF multimers were analyzed using the HYDRASYS-2 SCAN system and the HYDRAGEL 5- or 11-VW Multimer kits (Sebia). VWF activity levels were measured with the HemosIL Acustar VWF:GPIbR on the ACL Acustar Analyzer (IL). ResultsFor ADAMTS13 activity, a strong linear relationship and no bias between CLIA and ELISA were confirmed (slope=1.01 [0.91, 1.11], intercept=0.00 [-0.47, 0]). However, significant discrepancies were found in AAb detection during remission phases with ADAMTS13 activity between 10% and 50%, with CLIA and ELISA showing significant divergence (p < 0.001, Cohen’s g=0.34). Consistently, VWF multimers and activity levels exhibited significantly different values between remission samples with ADAMTS13 activity below 50% or above 50%. In longitudinal analysis of patients with multiple iTTP relapses, positivity to CLIA appear to precede ELISA in predicting exacerbations. ConclusionsWhile CLIA and ELISA might be interchangeable for assessing ADAMTS13 activity, they are not equivalent for detecting AAb, particularly in patients in clinical remission with ADAMTS13 activity between 10% and 50%.