論文 - 詳細
| RRC ID | 78662 |
|---|---|
| 著者 | Sakai K, Miyadera H, Kubo M, Nakajima F, Matsumoto M. |
| タイトル | Overlapping ADAMTS13 peptide binding profiles of DRB1∗08:03 and DRB1∗11:01 suggest a common etiology of immune-mediated thrombotic thrombocytopenic purpura. |
| ジャーナル | J Thromb Haemost |
| Abstract |
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. |
| 巻・号 | 21(3) |
| ページ | 616-628 |
| 公開日 | 2023-3-1 |
| DOI | 10.1016/j.jtha.2022.09.002 |
| PII | S1538-7836(22)07170-7 |
| PMID | 36696200 |
| MeSH | ADAMTS13 Protein / metabolism Autoantibodies Disease Susceptibility Epitopes, T-Lymphocyte* HLA-DRB1 Chains / immunology Humans Peptides / chemistry Purpura, Thrombotic Thrombocytopenic* |
| リソース情報 | |
| ヒト・動物細胞 | NIH3T3 |