PMID- 36696200
OWN - NLM
STAT- MEDLINE
DCOM- 20230308
LR  - 20230310
IS  - 1538-7836 (Electronic)
IS  - 1538-7836 (Linking)
VI  - 21
IP  - 3
DP  - 2023 Mar
TI  - Overlapping ADAMTS13 peptide binding profiles of DRB1 *08:03 and DRB1 *11:01 
      suggest a common etiology of immune-mediated thrombotic thrombocytopenic purpura.
PG  - 616-628
LID - S1538-7836(22)07170-7 [pii]
LID - 10.1016/j.jtha.2022.09.002 [doi]
AB  - BACKGROUND: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is an 
      ultra-rare autoimmune disorder caused by autoantibodies against ADAMTS13. A 
      strong association of DRB1 *11 with iTTP and DRB1 *11-restricted T-cell epitopes in 
      ADAMTS13 have been reported in Europeans, whereas we previously found DRB1 *08:03 
      as a susceptible allele in Japanese. OBJECTIVES: The limited information is 
      available regarding a susceptible allele and its T-cell epitopes in Japanese 
      patients with iTTP. MATERIALS AND METHODS: We conducted a reanalysis on 
      iTTP-predisposing alleles using 3 distinct Japanese control groups. Subsequently, 
      a novel human leukocyte antigen (HLA)-peptide expression assay (MHC-density 
      assay) was used to identify the presentation of 24 ADAMTS13-derived peptides, 
      including the regions that were identified previously by MHC-peptidome analysis 
      and/or T-cell assays or predicted by NetMHCIIpan-4.0, to DRB1 *08:03 and 
      DRB1 *11:01. RESULTS: We reconfirmed the strong association of DRB1 *08:03 with 
      iTTP, as well as the absence of the secondary risk alleles and protective alleles 
      in Japanese iTTP, which altogether reveal that the HLA association pattern is 
      completely different between the European and Japanese iTTP. MHC-density assay 
      found the 3 ADAMTS13-derived peptides in the spacer domain as a potential strong 
      binder to DRB1 *08:03. Moreover, 6 peptides in the metalloprotease, spacer, sixth 
      thrombospondin-1 repeat, and CUB domains in ADAMTS13 showed increased 
      presentation by both DRB1 *08:03 and DRB1 *11:01. CONCLUSION: Altogether, the 
      findings of distinct HLA-DR association with iTTP across populations and the 
      presentation of common peptides by DRB1 *08:03 and DRB1 *11:01 suggest that the 
      same ADAMTS13-derived peptides might be presented and trigger the activation of 
      autoreactive CD4(+) T cells, leading to production of anti-ADAMTS13 
      autoantibodies by autoreactive B cells.
CI  - Copyright (c) 2022 International Society on Thrombosis and Haemostasis. Published 
      by Elsevier Inc. All rights reserved.
FAU - Sakai, Kazuya
AU  - Sakai K
AD  - Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, 
      Japan.
FAU - Miyadera, Hiroko
AU  - Miyadera H
AD  - Department of Medical Genetics, Faculty of Medicine, University of Tsukuba, 
      Tsukuba, Japan.
FAU - Kubo, Masayuki
AU  - Kubo M
AD  - Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, 
      Japan.
FAU - Nakajima, Fumiaki
AU  - Nakajima F
AD  - GenoDive Pharma Inc, Atsugi, Japan.
FAU - Matsumoto, Masanori
AU  - Matsumoto M
AD  - Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, 
      Japan. Electronic address: mmatsumo@naramed-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221222
PL  - England
TA  - J Thromb Haemost
JT  - Journal of thrombosis and haemostasis : JTH
JID - 101170508
RN  - EC 3.4.24.87 (ADAMTS13 Protein)
RN  - EC 3.4.24.87 (ADAMTS13 protein, human)
RN  - 0 (Autoantibodies)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Peptides)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
CIN - J Thromb Haemost. 2023 Mar;21(3):456-459. PMID: 36858791
MH  - Humans
MH  - ADAMTS13 Protein/metabolism
MH  - Autoantibodies
MH  - Disease Susceptibility
MH  - *Epitopes, T-Lymphocyte
MH  - Peptides/chemistry
MH  - *Purpura, Thrombotic Thrombocytopenic
MH  - HLA-DRB1 Chains/immunology
OTO - NOTNLM
OT  - ADAMTS13 protein
OT  - HLA-DR antigens
OT  - T-cell epitopes
OT  - autoimmune disease
OT  - thrombotic thrombocytopenic purpura
EDAT- 2023/01/26 06:00
MHDA- 2023/03/04 06:00
CRDT- 2023/01/25 12:02
PHST- 2022/07/20 00:00 [received]
PHST- 2022/09/05 00:00 [revised]
PHST- 2022/09/23 00:00 [accepted]
PHST- 2023/01/26 06:00 [pubmed]
PHST- 2023/03/04 06:00 [medline]
PHST- 2023/01/25 12:02 [entrez]
AID - S1538-7836(22)07170-7 [pii]
AID - 10.1016/j.jtha.2022.09.002 [doi]
PST - ppublish
SO  - J Thromb Haemost. 2023 Mar;21(3):616-628. doi: 10.1016/j.jtha.2022.09.002. Epub 
      2022 Dec 22.