ADAMTS13-specific circulating immune complexes as potential predictors of relapse in patients with acquired thrombotic thrombocytopenic purpura

Background: Acquired thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy due to the development of autoantibodies against the VWF-cleaving protease ADAMTS13. ADAMTS13-specific circulating immune complexes (CICs) have been described in patients with acquired TTP, but their clinical relevance remained to be established. The aim of this study was to assess the association between ADAMTS13-specific CICs and ADAMTS13-related measurements, clinical and laboratory markers of disease severity, and occurrence of TTP relapse, in autoimmune TTP patients. Material and methods: We measured ADAMTS13-specific CICs in 51 patients with severe ADAMTS13 deficiency and anti-ADAMTS13 autoantibodies, at the first episode of acquired TTP. The associations between ADAMTS13-specific CICs and the variables of interest were assessed by linear, logistic and Cox proportional hazard regression models, where appropriate. Results: The prevalence of ADAMTS13-specific CICs in patients experiencing the first TTP episode was 39% (95% confidence intervals [CI]: 26-52%). ADAMTS13-specific CICs were not associated neither with laboratory markers of disease severity, nor with patterns of clinical presentation. Conversely, among 45 survivors, a positive association was found between the presence of ADAMTS13-specific CICs and the risk of recurrence within 2. years after the first TTP episode (adjusted hazard ratio, 3.4 [95% CI: 0.9 to 13.5]). Conclusions: ADAMTS13-specific CICs seem to be able to predict the recurrence of acute TTP episodes in the first 2. years after disease onset. Therefore, their measurement might be used as a tool to stratify the risk of disease relapse, with potential influence on surveillance and therapeutic choices during remission phase.