ADAMTS-13 Conformation

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy caused by an autoimmune-driven deficiency of ADAMTS-13. Despite remission, relapses remain a major concern for patients and are currently predicted by monitoring ADAMTS-13 activity.

Objectives: This study evaluated the association between ADAMTS-13 conformation and relapse risk in patients with iTTP during follow-up.

Methods: We conducted a retrospective monocentric study involving patients with iTTP with ADAMTS-13 monitoring from 2008 to 2020. ADAMTS-13 antigen and conformation were assessed in plasma samples using our 3H9-ELISA and 1C4-ELISA, respectively.

Results: Fifteen patients with iTTP were monitored for a median of 7 years (IQR, 6-11) with a total of 479 plasma samples. Based on annual relapse rate (RR; median, 0.5), they were categorized as low (group 1; RR, <0.50, n = 8) or high relapsers (group 2; RR, ≥0.50, n = 7). ADAMTS-13 activity normalized between iTTP relapses in all patients. However, the time from normalization with an open conformation to relapse was shorter in group 2 (5 vs 21 months; P < .001). Median annual ADAMTS-13 activity differ significantly between groups (54.1% vs 50.0%; P = .1893). A trend suggested greater time spent in an open conformation in group 2 (0.6 vs 0.2; P = .1427). Rituximab was effective in group 1, while group 2 patients often required alternative therapies.

Conclusion: Persistent open ADAMTS-13 conformation in remission samples was observed more frequently in patients with higher relapse risk and could potentially serve as a biomarker for detecting low levels of circulating autoantibodies. This potential biomarker requires prospective validation before it can be used to guide individualized iTTP management.