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

Ferrari, Silvia; Knöbl, Paul; Kolovratova, Vera; Plaimauer, Barbara; Turecek, Peter L.; Váradi, Katalin; Rottensteiner, Hanspeter; Scheiflinger, Friedrich

doi:10.1111/j.1538-7836.2011.04548.x

Cited by 20 publications

(23 citation statements)

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“…This is consistent with results for a previously described patient with refractory acquired TTP. 23 Furthermore, the inverse correlation between free and complexed anti-ADAMTS13 antibodies seen in this patient during treatment was also discernible for the three patients during the early acute event while on PEX. However, no clear such trend was found in remission.…”

Section: A B Cmentioning

confidence: 59%

“…An ELISA to detect total IgG-immune complexes was not established, however, the total amount of IgG-immune complexes was investigated in selected patients by co-immunoprecipitation, as described previously 23 (Online Supplementary Methods).…”

Section: Detection Of Adamts13-specific Immune Complexesmentioning

confidence: 99%

“…ADAMTS13-specific immune complexes were detected with a newly developed ELISA-based assay and, as a complementary method, a co-immunoprecipitation assay. 23 In the ELISA, a polyclonal anti-ADAMTS13 antibody was used to capture ADAMTS13-specific immune complexes present in plasma; the composition of the immunoglobulin fraction of the immune complexes was revealed by antibodies directed against human IgG1-4, IgM and IgA. A limitation of the ELISA set-up is that it only detects immune complexes bearing an ADAMTS13 molecule with accessible epitope(s) for the capturing antibody.…”

Section: A B Cmentioning

confidence: 99%

“…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. Results are discussed in terms of immune complexes as a novel biomarker that may contribute to a better understanding of the pathogenesis of acquired TTP and its responsiveness to treatment.…”

Section: Introductionmentioning

confidence: 99%

“…The next day, the immunoglobulin fraction of the bound immune complexes was detected with horseradish peroxidase-conjugated class-specific secondary antibodies followed by detection with an appropriate chromogenic substrate. For details, see Online Supplementary Methods and Online Supplementary Figure S1.An ELISA to detect total IgG-immune complexes was not established, however, the total amount of IgG-immune complexes was investigated in selected patients by co-immunoprecipitation, as described previously 23 (Online Supplementary Methods). …”

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

et al. 2013

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© F e r r a t a S t o r t i F o u n d a t i o nTTP. Sixty-eight patients were tested during the acute phase, with 48 patients experiencing their first acute episode and 20 a relapse. For 18 of these patients, corresponding samples in clinical remission were also available. Ten patients were analyzed only during remission, giving a total of 28 patients tested in remission. The patients' demographics and clinical features are summarized in Table 1. The inclusion criteria for patients with acute acquired TTP were: presence of severe ADAMTS13 deficiency (<10%), thrombocytopenia (platelet count <150x10 9 /L), microangiopathic hemolytic anemia (hemoglobin <12 g/dL) with presence of schistocytes on the peripheral blood smear, and elevated lactate dehydrogenase levels (>450 IU/L). Fever, neurological symptoms or renal failure were not mandatory. Remission was defined as a normal platelet count (>150x10 9 /L) and no plasma exchange treatment for ≥30 consecutive days. Relapse was defined as the reappearance of clinical manifestation and/or laboratory data compatible with TTP after remission.Frozen citrated plasma samples were obtained from four international centers. The study was approved by the ethic committees of the University Hospital of Berne, Switzerland; Medical University of Vienna, Austria; Lille University Hospital, France; and Icahn School of Medicine, New York, USA. ADAMTS13 assaysADAMTS13 activity (ADAMTS13:Ac) and ADAMTS13 functional inhibitor titers were measured using fluorometric FRETS-VWF73 assay as described elsewhere. 24,25 The limit of quantification of ADAMTS13:Ac was 0.05 U/mL (5%); values <0.10 U/mL (<10%) were considered severely reduced; levels of 0.10-0.50 U/mL as reduced and levels >0.5 U/mL as normal. An inhibitor titer <0.7 BU/mL was considered negative. Plasma ADAMTS13 antigen (ADAMTS13:Ag) levels were determined by ELISA as described previously. 20 The reference range of the assay was 403 -907 ng/mL; the limit of quantification was 10 ng/mL. Levels of 100 -403 ng/mL were considered reduced, levels <100 ng/mL as severely reduced, and values <10 ng/mL as undetectable. Detection of free anti-ADAMTS13 antibodies by enzyme-linked immunosorbent assayFree antibodies were detected as described elsewhere 25 with modifications (Online Supplementary Methods). Detection of ADAMTS13-specific immune complexesMicrotiter plates were coated with a polyclonal rabbit antihuman ADAMTS13 antibody. After blocking the non-specific sites, diluted patient's plasma samples and controls were added and incubated overnight at 4°C. The next day, the immunoglobulin fraction of the bound immune complexes was detected with horseradish peroxidase-conjugated class-specific secondary antibodies followed by detection with an appropriate chromogenic substrate. For details, see Online Supplementary Methods and Online Supplementary Figure S1.An ELISA to detect total IgG-immune complexes was not established, however, the total amount of IgG-immune complexes was investigated in selected patients by co-immunoprecipitation,...

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Section: A B Cmentioning

confidence: 59%

Section: Detection Of Adamts13-specific Immune Complexesmentioning

confidence: 99%

Section: A B Cmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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

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Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome

Hovinga

2017

Platelets in Thrombotic and Non-Thrombotic Disorders

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Correlation between ADAMTS13 activity and neurological impairment in acute thrombotic microangiopathy patients

Marinis

Novello

Ferrari

et al. 2016

J Thromb Thrombolysis

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Differential diagnosis between thrombotic thrombocytopenic purpura (TTP) and other thrombotic microangiopathies (TMA) is usually difficult because of frequently overlapping clinical presentations. Severely depressed ADAMTS13 activity (<10 %) seems distinctive for TTP because of its pathogenetic role. However a long debate exists in the literature about its sensibility and specificity. Our aim was to search for clinical differences between TMA patients referred to our laboratory, comparing them for protease activity <10 versus ≥10 %. ADAMTS13 activity ≥10 % patients (n = 73) showed a higher prevalence of drug- (p = 0.005) and cancer-associated (p < 0.001) TMA. Mean platelet count and renal dysfunction prevalence was lower (p < 0.001), while neurological impairment was more frequent (p = 0.001) in the <10 % ADAMTS13 activity group (n = 109), confirming previous literature findings. When taken neurological manifestations singularly, epilepsy (p = 0.04), focal motor deficit (p < 0.001) and cranial nerve palsy (p = 0.007) were more frequent in the <10 % activity group. In our case series, a <10 % ADAMTS13 activity depicts a group of patients with clinical features similar to TTP patients. Focal motor impairment or epileptic manifestations could further address toward a TTP diagnosis. Studies about treatment efficacy and follow-up are advised to determine whether laboratory findings can guide therapeutic decisions.

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

Cited by 20 publications

References 10 publications

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

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

Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome

Correlation between ADAMTS13 activity and neurological impairment in acute thrombotic microangiopathy patients

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