| Item type |
itemtype_ver1(1) |
| 公開日 |
2022-02-14 |
| タイトル |
|
|
タイトル |
Successful treatment of a novel type I interferonopathy due to a de novo PSMB9 gene mutation with a Janus kinase inhibitor |
|
言語 |
en |
| 著者 |
Kataoka, Shinsuke
Kawashima, Nozomu
Okuno, Yusuke
Muramatsu, Hideki
Miwata, Shunsuke
Narita, Kotaro
Hamada, Motoharu
Murakami, Norihiro
Taniguchi, Rieko
Ichikawa, Daisuke
Kitazawa, Hironobu
Suzuki, Kyogo
Nishikawa, Eri
Narita, Atsushi
Nishio, Nobuhiro
Yamamoto, Hidenori
Fukasawa, Yoshie
Kato, Taichi
Yamamoto, Hiroyuki
Natsume, Jun
Kojima, Seiji
Nishino, Ichizo
Taketani, Takeshi
Ohnishi, Hidenori
Takahashi, Yoshiyuki
|
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 権利 |
|
|
言語 |
en |
|
権利情報 |
© 2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
JAK inhibitor |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
interferonopathy |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
pulmonary hypertension |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
proteasome subunit beta type 9 (PSMB9) |
| 内容記述 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Background: Type I interferonopathies are a recently established subgroup of autoinflammatory diseases caused by mutations in genes associated with proteasome degradation or cytoplasmic RNA- and DNA-sensing pathways. Objective: This study aimed to unveil the molecular pathogenesis of a patient with novel type I interferonopathy, for which no known genetic mutations have been identified. Methods: We performed the whole-exome sequencing of a 1-month-old boy with novel type I interferonopathy. We also investigated proteasome activities using patient-derived B lymphoblastoid cell lines (LCLs) and normal LCLs transduced with the mutant gene. Results: Whole-exome sequencing identified a de novo proteasome 20S subunit beta 9 (PSMB9) p.G156D mutation in the patient who developed fever, a chilblain-like skin rash, myositis, and severe pulmonary hypertension due to the hyperactivation of IFN-α. Patient-derived LCLs revealed reduced proteasome activities, and exogenous transduction of mutant PSMB9 p.G156D into normal LCLs significantly suppressed proteasome activities, and the endogenous PSMB9 protein was lost along with the reduction of other immunoproteasome subunits, PSMB8 and PSMB10 proteins. He responded to the administration of a Janus kinase inhibitor, tofacitinib, and he was successfully withdrawn from venoarterial extracorporeal membranous oxygenation. At age 7 months, he received an unrelated cord blood transplantation. At 2 years posttransplantation, he no longer required tofacitinib and experienced no disease recurrence. Conclusions: We present the case of a patient with a novel type I interferonopathy caused by a de novo PSMB9 p.G156D mutation that suppressed the wild-type PSMB9 protein expression. Janus kinase inhibitor and stem cell transplantation could be curative therapies in patients with severe interferonopathies. |
|
言語 |
en |
| 出版者 |
|
|
出版者 |
Elsevier |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプresource |
http://purl.org/coar/resource_type/c_6501 |
|
タイプ |
journal article |
| 出版タイプ |
|
|
出版タイプ |
AM |
|
出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
| 関連情報 |
|
|
関連タイプ |
isVersionOf |
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1016/j.jaci.2021.03.010 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
PISSN |
|
収録物識別子 |
0091-6749 |
| 書誌情報 |
en : Journal of Allergy and Clinical Immunology
巻 148,
号 2,
p. 639-644,
発行日 2021-08
|
| ファイル公開日 |
|
|
日付 |
2022-08-01 |
|
日付タイプ |
Available |
CM_FinalFile_PSMB9_manuscript.pdf (1.8 MB)
