Ruxolitinib: Targeted Approach for Treatment of Autoinflammatory Very Early Onset Inflammatory Bowel Disease.
Ruxolitinib: Targeted Approach for Treatment of Autoinflammatory Very Early Onset Inflammatory Bowel Disease.
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DOI：
10.1016/j.cgh.2021.07.040
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发表时间：
2022-06
期刊：
影响因子：
--
通讯作者：
Kelsen JR
中科院分区：
文献类型：
--
作者：
Rudra S;Shaul E;Conrad M;Patel T;Moore A;Dawany N;Canavan MC;Sullivan KE;Behrens E;Kelsen JR
在小于6岁时诊断的极早发性炎症性肠病（VEO-IBD）在遗传和表型上可以是不同的，并且比老年发病的IBD更难治。在VEO-IBD的一小部分中，已确定的因果性单基因缺陷已被治疗靶向（1），然而对于大多数这些儿童，迫切需要治疗策略如表型谱来改善结果。在VEO-IBD儿童中确定的> 70种单基因缺陷中的大多数涉及免疫应答和上皮屏障功能（1，2），包括JAK-STAT途径的异常激活和干扰素（IFN）介导的自身炎性疾病（AID）（3，4）。这种表型的特征是反复发热、炎症标志物升高、细胞因子产生增加以及严重的肠道和全身性疾病（2）。针对IFN产生的治疗在一些AIDS中显示出有希望的结果（5）。Ruxolitinib是一种选择性JAK 1/2抑制剂，被批准用于治疗真性红细胞增多症、骨髓纤维化和移植物抗宿主病。它还显示出在免疫失调疾病中的潜力，例如由STAT 1和STAT 3 GOF突变引起的干扰素病（6，7）。虽然对肠道症状的疗效尚未确定（8），但我们假设它对具有自身炎症表型（AIP）的VEO-IBD患者有效。
Very early onset-inflammatory bowel disease (VEO-IBD), diagnosed< 6 years old, can be genetically and phenotypically distinct and more refractory than older-onset IBD. Identified causal monogenic defects have been targeted therapeutically in a small subset of VEO-IBD (1), however for the majority of these children, treatment strategies such as phenotypic profiles are critically needed to improve outcomes.Most of the> 70 monogenic defects identified in children with VEO-IBD involve immune response and epithelial barrier function (1, 2), including aberrant activation of the JAK-STAT pathway and interferon (IFN)-mediated autoinflammatory disease (AID)(3, 4). This phenotype is characterized by recurrent fevers, elevated inflammatory markers, increased cytokine production, and severe intestinal and systemic disease (2). Therapies targeted to IFN production have shown promising results in some AIDs (5). Ruxolitinib, a selective JAK1/2 inhibitor, is approved to treat polycythemia vera, myelofibrosis, and graft versus host disease. It has also shown potential in immune dysregulation disorders such as interferonopathies caused by STAT1 and STAT3 GOF mutations (6, 7). While efficacy for intestinal symptoms has not been established (8), we hypothesized it would be effective in patients with VEO-IBD who have an autoinflammatory phenotype (AIP).
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影响因子：
29.4
作者：
Uhlig HH;Schwerd T;Koletzko S;Shah N;Kammermeier J;Elkadri A;Ouahed J;Wilson DC;Travis SP;Turner D;Klein C;Snapper SB;Muise AM;COLORS in IBD Study Group and NEOPICS
通讯作者：
COLORS in IBD Study Group and NEOPICS
DOI：
10.1097/mpg.0000000000002567
发表时间：
2020-03-01
影响因子：
2.9
作者：
Kelsen, Judith R.;Sullivan, Kathleen E.;Grossman, Andrew B.
通讯作者：
Grossman, Andrew B.
影响因子：
8
作者：
Li Jianguo;Zhou Zhixuan;Shi Xiaodong
通讯作者：
Shi Xiaodong
影响因子：
20.3
作者：
Toubiana, Julie;Okada, Satoshi;Netea, Mihai G.
通讯作者：
Netea, Mihai G.
影响因子：
14.2
作者：
Forbes, Lisa R.;Vogel, Tiphanie P.;Leiding, Jennifer W.
通讯作者：
Leiding, Jennifer W.