scholarly journals Generation and validation of small ADAMTS13 fragments for epitope mapping of anti‐ADAMTS13 autoantibodies in immune‐mediated thrombotic thrombocytopenic purpura

2020 ◽  
Vol 4 (5) ◽  
pp. 918-930
Author(s):  
Kadri Kangro ◽  
Elien Roose ◽  
An‐Sofie Schelpe ◽  
Edwige Tellier ◽  
Gilles Kaplanski ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Epitope Mapping ◽  
Thrombocytopenic Purpura ◽  
Immune Mediated

scholarly journals Anti-ADAMTS13 autoantibody profiling in patients with immune-mediated thrombotic thrombocytopenic purpura

2021 ◽  
Vol 5 (17) ◽  
pp. 3427-3435 ◽  
Author(s):  
Kadri Kangro ◽  
Elien Roose ◽  
Bérangère S. Joly ◽  
György Sinkovits ◽  
Tanja Falter ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Acute Phase ◽  
Clinical Data ◽  
Epitope Mapping ◽  
Thrombocytopenic Purpura ◽  
Immune Mediated ◽  
Number Of Patients ◽  
Large Cohort Study ◽  
A Disintegrin And Metalloproteinase

Abstract Anti-A Disintegrin and Metalloproteinase with a ThromboSpondin type 1 motif, member 13 (ADAMTS13) autoantibodies cause a severe ADAMTS13 deficiency in immune-mediated thrombotic thrombocytopenic purpura (iTTP). ADAMTS13 consists of a metalloprotease (M), a disintegrin-like (D) domain, 8 thrombospondin type 1 repeats (T1-T8), a cysteine-rich (C), a spacer (S), and 2 CUB domains (CUB1-2). We recently developed a high-throughput epitope mapping assay based on small, nonoverlapping ADAMTS13 fragments (M, DT, CS, T2-T5, T6-T8, CUB1-2). With this assay, we performed a comprehensive epitope mapping using 131 acute-phase samples and for the first time a large group of remission samples (n = 50). Next, samples were stratified according to their immunoprofiles, a field that is largely unexplored in iTTP. Three dominant immunoprofiles were found in acute-phase samples: profile 1: only anti-CS autoantibodies (26.7%); profile 2: both anti-CS and anti-CUB1-2 autoantibodies (12.2%); and profile 3: anti-DT, anti-CS, anti-T2-T5, anti-T6-T8, and anti-CUB1-2 autoantibodies (8.4%). Interestingly, profile 1 was the only dominant immunoprofile in remission samples (52.0%). Clinical data were available for a relatively small number of patients with acute iTTP (>68), and no correlation was found between immunoprofiles and disease severity. Nevertheless, profile 1 was linked with younger and anti-T2-T5 autoantibodies with older age and the absence of anti-CUB1-2 autoantibodies with cerebral involvement. In conclusion, identifying acute phase and remission immunoprofiles in iTTP revealed that anti-CS autoantibodies seem to persist or reappear during remission providing further support for the clinical development of a targeted anti-CS autoantibody therapy. A large cohort study with acute iTTP samples will validate possible links between immunoprofiles or anti-domain autoantibodies and clinical data.

Dasatinib-induced immune mediated-thrombotic thrombocytopenic purpura

2018 ◽  
Vol 57 (2) ◽  
pp. 222-224 ◽  
Author(s):  
Esra Terzi Demirsoy ◽  
Ozgur Mehtap ◽  
Elif Birtas Atesoglu ◽  
Pinar Tarkun ◽  
Necmi Eren ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Immune Mediated

scholarly journals The HLA Variant rs6903608 Is Associated with Disease Onset and Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura in Caucasians

2020 ◽  
Vol 9 (10) ◽  
pp. 3379
Author(s):  
Ilaria Mancini ◽  
Elisa Giacomini ◽  
Silvia Pontiggia ◽  
Andrea Artoni ◽  
Barbara Ferrari ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Risk Allele ◽  
Absolute Risk ◽  
Disease Onset ◽  
Close Monitoring ◽  
Reference Allele ◽  
Thrombocytopenic Purpura ◽  
Immune Mediated ◽  
The Impact ◽  
Risk Of Relapse

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening thrombotic microangiopathy caused by severe ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13) deficiency, recurring in 30–50% of patients. The common human leukocyte antigen (HLA) variant rs6903608 was found to be associated with prevalent iTTP, but whether this variant is associated with disease relapse is unknown. To estimate the impact of rs6903608 on iTTP onset and relapse, we performed a case-control and cohort study in 161 Italian patients with a first iTTP episode between 2002 and 2018, and in 456 Italian controls. Variation in rs6903608 was strongly associated with iTTP onset (homozygotes odds ratio (OR) 4.68 (95% confidence interval (CI) 2.67 to 8.23); heterozygotes OR 1.64 (95%CI 0.95 to 2.83)), which occurred over three years earlier for each extra risk allele (β −3.34, 95%CI −6.69 to 0.02). Of 153 survivors (median follow-up 4.9 years (95%CI 3.7 to 6.1)), 44 (29%) relapsed. The risk allele homozygotes had a 46% (95%CI 36 to 57%) absolute risk of relapse by year 6, which was significantly higher than both heterozygotes (22% (95%CI 16 to 29%)) and reference allele homozygotes (30% (95%CI 23 to 39%)). In conclusion, HLA variant rs6903608 is a risk factor for both iTTP onset and relapse. This newly identified biomarker may help with recognizing patients at high risk of relapse, who would benefit from close monitoring or intensified immunosuppressive therapy.

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

Blood ◽  
2017 ◽  
Vol 130 (4) ◽  
pp. 466-471 ◽  
Author(s):  
Ferras Alwan ◽  
Chiara Vendramin ◽  
Karen Vanhoorelbeke ◽  
Katy Langley ◽  
Vickie McDonald ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Fold Increase ◽  
Thrombocytopenic Purpura ◽  
Immune Mediated ◽  
Key Points

Key Points High anti-ADAMTS13 antibody and low ADAMTS13 antigen levels adversely affect outcome in immune-mediated TTP with greater mortality seen. A raised troponin at presentation confers a sixfold increase and reduced GCS a nine-fold increase in mortality in acute TTP.

scholarly journals Systemic Lupus Erythematosus Presenting as Thrombotic Thrombocytopenia Purpura: How Close Is Close Enough?

2011 ◽  
Vol 2011 ◽  
pp. 1-3 ◽  
Author(s):  
Cesar A. Perez ◽  
Nabil Abdo ◽  
Anuj Shrestha ◽  
Edgardo S. Santos
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Laboratory Findings ◽  
Thrombocytopenic Purpura ◽  
Double Stranded Dna ◽  
Immune Mediated ◽  
Healthy Female ◽  
Life Threatening

Thrombotic thrombocytopenic purpura (TTP) is an uncommon life-threatening disease characterized by microangiopathic hemolytic anemia and thrombocytopenia, commonly associated with infections, malignancy, drugs, and autoimmune diseases. We report a case of 19-year-old previously healthy female that presents with anemia and thrombocytopenia diagnosed with thrombotic thrombocytopenic purpura that was treated successfully with plasmapheresis and corticosteroids. Laboratory findings also revealed antinuclear antibodies and antibodies to double-stranded DNA. Two weeks after presentation developed inflammatory arthritis, fulfilling diagnostic criteria for systemic lupus erythematosus (SLE). Prompt diagnosis and treatment with plasma exchange and corticosteroids should be instituted as soon as the diagnosis of TTP is suspected, even if other diagnoses, including lupus, are possible. When present, the coexistence of these two etiologies can have a higher mortality than either disease alone. An underlying diagnosis of SLE should be considered in all patients presenting TTP and the study of this association may provide a better understanding of their immune-mediated pathophysiology.

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