ADAMTS13 activity and antigen during therapy and follow-up of patients with idiopathic thrombotic thrombocytopenic purpura: correlation with clinical outcome

Abstract

BackgroundThe assay for ADAMTS13 activity helps clinicians to confirm the clinical diagnosis of idiopathic thrombotic thrombocytopenic purpura. The clinical value of testing for the antigen level of ADAMTS13 protein is, however, less clear. Design and MethodsIn this study, both ADAMTS13 antigen and activity levels were measured in 835 sequential samples from 40 consecutive patients who were followed for an average of 29 months throughout the course of acute episode plasma exchange treatment and clinical remission. ResultsDuring acute episodes, ADAMTS13 activity was severely deficient while ADAMTS13 antigen levels were more variable, ranging from severely deficient to as high as within the reference range. A severe depletion of ADAMTS13 antigen level during acute disease was, however, statistically associated with disease mortality (P=0.0322). For patients who achieved initial clinical responses, ADAMTS13 antigen levels appeared to be restored faster than ADAMTS13 activity to the normal range. Further analysis demonstrated that the ADAMTS13 antigen level at the time of initial clinical recovery was significantly higher in the patients who subsequently achieved a sustained clinical remission than in the group who soon after had an exacerbation (P=0.0187). ConclusionsOur data suggest that evaluation of ADAMTS13 antigen levels during the course of therapy and follow-up may offer additional useful information for the management of patients with thrombotic thrombocytopenic purpura.Key words: thrombotic thrombocytopenic purpura, ADAMTS13, prognosis, biomarker.Citation: Yang S, Jin M, Lin S, Cataland S, and Wu H. ADAMTS13 activity and antigen during therapy and follow-up of patients with idiopathic thrombotic thrombocytopenic purpura: correlation with clinical outcome Haematologica 2011;96(10)

Persistence of circulating ADAMTS13-specific immune complexes in patients with acquired thrombotic thrombocytopenic purpura

“…By contrast, previously employed methods detected immune complexes only indirectly by measuring ADAMTS13:Ag or ADAMTS13:Ac in IgG-depleted plasma 20,21 or by a poorly reported direct detection of the IgG antibody portion of the ADAMTS13-immune complexes using a commercial kit to quantify ADAMTS13:Ag levels in a limited number of patients. 22 The most relevant finding of our study was the detection of IgG-immune complexes in 93% of patients in remission, independently of the duration of the remission. This strongly indicates that ADAMTS13-specific immune complexes circulate in patients with acquired TTP patients throughout the entire course of the disease and many years after clinical remission.…”

“…17,18 With the isolation of inhibiting IgG antibodies against ADAMTS13 from plasma of TTP patients, the presence of ADAMTS13-specific immune complexes became plausible, 19 with the following observations supporting their existence: (i) removal of anti-ADAMTS13 IgG antibodies also removed measurable residual ADAMTS13 antigen; 20 (ii) residual ADAMTS13 activity was no longer measurable after plasma IgG depletion; 21 and (iii) human IgG bound to ADAMTS13 were identified by adaptation of a commercial ADAMTS13 antigen enzymelinked immunosorbent assay (ELISA). 22 Recently, we demonstrated the presence of ADAMTS13-specific immune complexes in a patient with refractory acquired TTP using a co-immunoprecipitation technique. 23 This observation prompted us to investigate the prevalence of ADAMTS13-specific immune complexes in a large cohort of patients with acquired TTP during the acute phase and in remission.…”

Presenting ADAMTS13 antibody and antigen levels predict prognosis in immune-mediated thrombotic thrombocytopenic purpura

“…20 The role of ADAMTS13 antigen levels in TTP is even less well characterized; however, emerging evidence suggests depletion of the ADAMTS13 antigen may be the dominant pathologic mechanism 21 and its levels a significant prognostic indicator. 22 Using the UK TTP registry, we have investigated whether the presenting levels of anti-ADAMTS13 IgG antibody and ADAMTS13 antigen had any effect on the mortality of patients presenting with acute TTP. As other studies have suggested, with a raised cardiac troponin level 13,14 and neurological involvement 10,12 as poor prognostic markers, these were also included in our investigation of risk factors for mortality in acute TTP.…”

Inverse correlation of free and immune complex‐sequestered anti‐ADAMTS13 antibodies in a patient with acquired thrombotic thrombocytopenic purpura

“…However, the extent to which these antibodies circulate in plasma in their free form or as a complex with ADAMTS13 and how this proportion changes over time is unclear. We and others have recently reported indirect detection by an ADAMTS13 antigen (ADAMTS13:Ag) ELISA of IgG ADAMTS13‐specific immune complexes (ICs) in plasma from patients with acquired TTP [5,6]. In the present study we used another more direct method for detecting ICs and compared the levels of free anti‐ADAMTS13 antibodies, ADAMTS13:Ag, ADAMTS13 activity (ADAMTS13:Ac) and inhibitor with those of ICs.…”