TY - JOUR
T1 - Anti-ADAMTS13 autoantibody profiling in patients with immune-mediated thrombotic thrombocytopenic purpura
AU - Kangro, Kadri
AU - Roose, Elien
AU - Joly, B. rangere S.
AU - Sinkovits, György
AU - Falter, Tanja
AU - von Auer, Charis
AU - Rossmann, Heidi
AU - Reti, Marienn
AU - Voorberg, Jan
AU - Prohászka, Zoltán
AU - Lämmle, Bernhard
AU - Coppo, Paul
AU - Veyradier, Agnès
AU - de Meyer, Simon F.
AU - Männik, Andres
AU - Vanhoorelbeke, Karen
N1 - Funding Information: This work was supported by the funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement No. 675746, and by the Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary, within the framework of the molecular biology thematic program of the Semmelweis University. Publisher Copyright: © 2021 by The American Society of Hematology
PY - 2021/9/14
Y1 - 2021/9/14
N2 - 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 5 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 antiCUB1-2 autoantibodies (8.4%). Interestingly, profile 1 was the only dominant immunopro-file 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.
AB - 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 5 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 antiCUB1-2 autoantibodies (8.4%). Interestingly, profile 1 was the only dominant immunopro-file 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.
UR - http://www.scopus.com/inward/record.url?scp=85115355882&partnerID=8YFLogxK
U2 - https://doi.org/10.1182/BLOODADVANCES.2020004172
DO - https://doi.org/10.1182/BLOODADVANCES.2020004172
M3 - Article
C2 - 34495312
SN - 2473-9529
VL - 5
SP - 3427
EP - 3435
JO - Blood advances
JF - Blood advances
IS - 17
ER -