Clinical implications of ADAMTS13 conformation ELISA in immune-mediated TTP with undetectable ADAMTS13 antigen.

BACKGROUND: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a fatal thrombotic disorder caused by anti-ADAMTS13 autoantibodies. ADAMTS13 conformation is a promising biomarker for diagnosing and monitoring iTTP; however, its utility in Japanese patients is limited owing to undetectable acute-phase ADAMTS13 antigen levels. OBJECTIVES: This study aimed to investigate if ADAMTS13 conformational changes can be detected even when ADAMTS13 antigen levels are undetectable for conventional assays. PATIENTS/METHODS: In this retrospective study, samples were obtained at initial presentation from 25 Japanese patients with acute iTTP and 21 healthy donors. We used purified patient IgGs to open up closed ADAMTS13 in normal plasma (patient IgG-based conformation enzyme-linked immunosorbent assay [ELISA]). The conformation index cutoff was 0.3 for the patient IgG-based assay. Conventional conformation ELISA was also performed when antigen levels were ≥0.03 mg/mL. RESULTS: The patient IgG-based assay demonstrated a closed-to-open conformational shift in all patients, enabling acute-phase assessment irrespective of antigen levels. Only 9 patients met the antigen threshold required for the conventional assay, and all demonstrated an open conformation. Over a median follow-up of 283 days, 5 patients experienced clinical relapse. Four patients showed an open conformation prior to relapse in both assays. When antigen levels were measurable, the patient IgG-based assay showed high concordance with the conventional assay. CONCLUSIONS: The patient IgG-based assay may help overcome the limitation imposed by low antigen levels during the acute phase in most Japanese patients with iTTP, enabling conformational assessment at presentation. Conformation ELISA may be useful for predicting relapse in Japanese patients with iTTP.