Relevance of ADAMTS13 antigenic levels in the characterization of pathological mechanisms associated with immune-mediated thrombotic thrombocytopenic purpura (iTTP)

CASTERA, SANTIAGO; ALBERTO, MARÍA FABIANA; WOODS, ADRIANA INÉS; DOS SANTOS, CÉLIA; TRINIDAD, JESICA; SÁNCHEZ-LUCEROS, ANALÍA

Congreso; ISTH 2023 Congress; 2023

rare and life-threatening autoimmune disease associated to severeADAMTS13 functional deficiency mediated by anti-ADAMTS13 antibodies.Laboratory diagnosis is based on the determination of ADAMTS13 enzymeactivity < 10 IU/dL and the concomitant presence of anti-ADAMTS13,predominantly the IgG isotype. Determination of ADAMTS13 antigen isusually not performed but may help identify whether enzyme deficiency isdue to functional abnormality and/or increased clearance.Aims: To determine ADAMTS13 antigen levels in a group of patients withacute iTTP.Methods: Citrated plasma samples from a sequential cohort of 35 patientswith acute iTTP, referred to our center between 2020 and 2021, were testedfor ADAMTS13 Activity, anti-ADAMTS13 IgG, ADAMTS13 antigen bycommercial ELISA methods (Technoclone) and VWF:Ag by an in houseELISA. All samples were processed before starting treatment (plasmaexchange and/or rituximab).Results: The clinical and laboratory characteristics are summarized inTable 1. Eighty percent of patients were female. Neurological symptomswere predominantly observed (70%), followed by gastrointestinal (21%) andrenal manifestations (9%). All patients presented ADAMTS13 activity < 5 IU/dL and anti-ADAMTS13 IgG > 14 U/mL. Interestingly, ADAMTS13 antigenwas highly reduced (median 7 IU/dL, range 2–32) with 94% of samples under20 IU/dL and 100% below normal range [Figure 1A], suggesting autoantibody-mediated ADAMTS13 clearance as a major pathogenic mechanism.Thiswas emphasized by a negative correlation between ADAMTS13 antigenlevels and anti-ADAMTS13 IgG titers (−0.57, p = 0.0003) [Figure 1B].Conclusion(s): In our cohort of iTTP patients, ADAMTS13 antigen levelsshowed that ADAMTS13 antigen depletion rather than enzyme inhibition isa dominant pathogenic mechanism, in accordance with previous report(Thomas MR, 2015). Routine assessment of ADAMTS13 antigen could beuseful to interpret the response to therapeutics in a more rational way.