The Role of ADAMTS13-Specific Circulating Immune Complexes in Prediction of Recurrence of Acquired Thrombotic Thrombocytopenic Purpura

Introduction. Acquired thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy due to the development of autoantibodies against the VWF-cleaving protease ADAMTS13. We recently developed and validated a new ELISA method for the detection of ADAMTS13-specific circulating immune complexes (CICs) in acquired TTP patients. This study aims at investigating the clinical relevance of ADAMTS13-specific CICs at disease presentation in a large cohort of acquired TTP patients.

Methods. We measured ADAMTS13-specific CICs by ELISA in 51 patients from the Milan TTP Registry, at the first episode of acquired TTP. All patients presented anti-ADAMTS13 autoantibodies by western blotting and severe ADAMTS13 deficiency (i.e., <10% of normal) by FRETS-VWF73 or CBA assays. We studied the associations between ADAMTS13-specific CICs levels and (i) ADAMTS13-related measurements (i.e., ADAMTS13 antigen, anti-ADAMTS13 IgG), (ii) clinical and laboratory markers of disease severity (i.e., muco-cutaneous bleeding, neurological, renal and cardiovascular symptoms, number of platelets, LDH, hemoglobin, creatinine), (iii) short- and long-term clinical outcomes (i.e., number of plasma exchange procedures required to attain remission, recurrence). Statistical analyses were performed using linear, logistic and Cox regression models.

Results. The prevalence of ADAMTS13-specific CICs in patients experiencing a first episode of acquired TTP was 39% (95% confidence intervals [CI]: 26-52%). ADAMTS13-specific CICs were only associated with ADAMTS13 antigen levels at regression analyses (beta per 10% increase in ADAMTS13 antigen, 95% CI: 0.05, 0.02-0.08). The presence of ADAMTS13-specific CICs was associated with more than a four-fold increase in the risk of recurrence at 2 years after the first TTP episode (hazard ratio, 95%CI: 4.2, 1.1-16.4).

Conclusions. ADAMTS13-specific CICs are neither a biomarker of disease severity, nor a predictor of clinical outcome during acute phase. Conversely, ADAMTS13-specific CICs seem to have relevance in predicting the recurrence of acute TTP episodes.