Assessment of type I interferon signatures in undifferentiated inflammatory diseases: A Japanese multicenter experience.
Assessment of type I interferon signatures in undifferentiated inflammatory diseases: A Japanese multicenter experience.
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DOI：
10.3389/fimmu.2022.905960
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发表时间：
2022
影响因子：
7.3
通讯作者：
Yasumi, Takahiro
中科院分区：
文献类型：
--
作者：
Miyamoto, Takayuki;Honda, Yoshitaka;Izawa, Kazushi;Kanazawa, Nobuo;Kadowaki, Saori;Ohnishi, Hidenori;Fujimoto, Masakazu;Kambe, Naotomo;Kase, Naoya;Shiba, Takeshi;Nakagishi, Yasuo;Akizuki, Shuji;Murakami, Kosaku;Bamba, Masahiro;Nishida, Yutaka;Inui, Ayano;Fujisawa, Tomoo;Nishida, Daisuke;Iwata, Naomi;Otsubo, Yoshikazu;Ishimori, Shingo;Nishikori, Momoko;Tanizawa, Kiminobu;Nakamura, Tomoyuki;Ueda, Takeshi;Ohwada, Yoko;Tsuyusaki, Yu;Shimizu, Masaki;Ebato, Takasuke;Iwao, Kousho;Kubo, Akiharu;Kawai, Toshinao;Matsubayashi, Tadashi;Miyazaki, Tatsuhiko;Kanayama, Tomohiro;Nishitani-Isa, Masahiko;Nihira, Hiroshi;Abe, Junya;Tanaka, Takayuki;Hiejima, Eitaro;Okada, Satoshi;Ohara, Osamu;Saito, Megumu K.;Takita, Junko;Nishikomori, Ryuta;Yasumi, Takahiro
关键词：
I型干扰素（IFN）信号转导的上调在炎性疾病中已被越来越多地检测到。最近，IFN信号的上调已被认为是IFN驱动的炎性疾病的潜在生物标志物。然而，目前还不清楚在何种程度上I型IFN参与未分化炎症性疾病的发病机制。本研究旨在量化临床未诊断患者的I型IFN特征，并评估具有高IFN特征的患者的临床特征。在患者的全血细胞中测量I型IFN特征。回顾性收集临床和生物学数据，并在具有高IFN特征的未确诊患者中进行密集的遗传分析。共分析了94例炎症性疾病患者的117份样本，其中包括37例未确诊病例。在19例未确诊的患者中观察到IFN信号增加，其中10例表现出I型干扰素病常见的临床特征。在8例患者中观察到的皮肤表现在宏观和组织学上与蛋白酶体相关自身炎症综合征中发现的相似。遗传分析确定了一名患者的PSMB 8基因中的新突变，以及四名患者中与I型IFN信号传导相关的基因中未知意义的罕见变异。JAK抑制剂有效地治疗了具有PSMB 8突变的患者。临床静止期特发性肺含铁血黄素沉着症和A20单倍不足患者IFN信号增强。在这项研究中，一半的患者检查，未分化的炎症性疾病，临床静止A20单倍不足，或特发性肺含铁血黄素沉着症，有一个升高的I型IFN签名。
Upregulation of type I interferon (IFN) signaling has been increasingly detected in inflammatory diseases. Recently, upregulation of the IFN signature has been suggested as a potential biomarker of IFN-driven inflammatory diseases. Yet, it remains unclear to what extent type I IFN is involved in the pathogenesis of undifferentiated inflammatory diseases. This study aimed to quantify the type I IFN signature in clinically undiagnosed patients and assess clinical characteristics in those with a high IFN signature. The type I IFN signature was measured in patients’ whole blood cells. Clinical and biological data were collected retrospectively, and an intensive genetic analysis was performed in undiagnosed patients with a high IFN signature. A total of 117 samples from 94 patients with inflammatory diseases, including 37 undiagnosed cases, were analyzed. Increased IFN signaling was observed in 19 undiagnosed patients, with 10 exhibiting clinical features commonly found in type I interferonopathies. Skin manifestations, observed in eight patients, were macroscopically and histologically similar to those found in proteasome-associated autoinflammatory syndrome. Genetic analysis identified novel mutations in the PSMB8 gene of one patient, and rare variants of unknown significance in genes linked to type I IFN signaling in four patients. A JAK inhibitor effectively treated the patient with the PSMB8 mutations. Patients with clinically quiescent idiopathic pulmonary hemosiderosis and A20 haploinsufficiency showed enhanced IFN signaling. Half of the patients examined in this study, with undifferentiated inflammatory diseases, clinically quiescent A20 haploinsufficiency, or idiopathic pulmonary hemosiderosis, had an elevated type I IFN signature.
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影响因子：
6.7
作者：
Kim, Hanna;Brooks, Kristina M.;Goldbach-Mansky, Raphaela
通讯作者：
Goldbach-Mansky, Raphaela
影响因子：
27.4
作者：
Landolt-Marticorena, C.;Bonventi, G.;Wither, J.
通讯作者：
Wither, J.
影响因子：
6
作者：
Biolato M;Bianco A;Lucchini M;Gasbarrini A;Mirabella M;Grieco A
通讯作者：
Grieco A
影响因子：
5
作者：
Kerrigan SA;McInnes IB
通讯作者：
McInnes IB
DOI：
10.1084/jem.20021553
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者：
Pascual V