CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease.
CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease.
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DOI：
10.1038/s41467-022-34873-7
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发表时间：
2022-11-24
影响因子：
16.6
通讯作者：
Fajgenbaum, David C.
中科院分区：
文献类型：
--
作者：
Pierson, Sheila K.;Katz, Laura;Williams, Reece;Mumau, Melanie;Gonzalez, Michael;Guzman, Stacy;Rubenstein, Ayelet;Oromendia, Ana B.;Beineke, Philip;Fossa, Alexander;van Rhee, Frits;Fajgenbaum, David C.
特发性多中心卡斯尔曼病（iMCD）是一种罕见且知之甚少的细胞因子风暴驱动的炎症性疾病。白细胞介素 6 (IL-6) 是某些患者已知的疾病驱动因素，但西妥昔单抗抗 IL-6 治疗并非对所有患者都有效，并且缺乏在治疗开始后的早期时间点表明成功的生物标志物。在这里，我们通过比较健康参与者 (N = 42)、iMCD 患者 (N = 88) 和相关疾病 (N = 60) 血清中 1,178 种蛋白质的水平，展示了候选疾病介质和西妥昔单抗反应预测因子的综合情况。 C-X-C Motif Chemokine Ligand-13 (CXCL13) 被鉴定和验证为 iMCD 中上调最显着的蛋白质。 CXCL13 水平的早期显着下降清楚地区分了西妥昔单抗应答者和无应答者；开始siltuximab治疗后第8天减少17%可预测稍后时间点的反应。因此，我们的研究表明 CXCL13 是 iMCD 中对 siltuximab 反应的预测生物标志物。特发性多中心 Castleman 病 (iMCD) 是一种危及生命的炎症性疾病，需要立即干预，推荐的一线治疗方法是白细胞介素 6 通路抑制剂西妥昔单抗 (siltuximab)。作者在此表明，开始siltuximab 治疗后不久，趋化因子CXCL13 水平的变化可以预测疗效。
Idiopathic multicentric Castleman disease (iMCD) is a rare and poorly-understood cytokine storm-driven inflammatory disorder. Interleukin-6 (IL-6) is a known disease driver in some patients, but anti-IL-6 therapy with siltuximab is not effective in all patients, and biomarkers indicating success at an early time point following treatment initiation are lacking. Here we show, by comparison of levels of 1,178 proteins in sera of healthy participants (N = 42), patients with iMCD (N = 88), and with related diseases (N = 60), a comprehensive landscape of candidate disease mediators and predictors of siltuximab response. C-X-C Motif Chemokine Ligand-13 (CXCL13) is identified and validated as the protein most prominently up-regulated in iMCD. Early and significant decrease in CXCL13 levels clearly distinguishes siltuximab responders from non-responders; a 17% reduction by day 8 following siltuximab therapy initiation is predictive of response at later time points. Our study thus suggests that CXCL13 is a predictive biomarker of response to siltuximab in iMCD. Idiopathic multicentric Castleman disease (iMCD) is a life-threatening inflammatory disease requiring immediate intervention, for which the recommended first-line therapy is the Interleukin-6 pathway inhibitor siltuximab. Authors here show that the change in levels of the chemokine CXCL13 shortly following the start of siltuximab treatment is predictive of response.
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影响因子：
3
作者：
Klimatcheva E;Pandina T;Reilly C;Torno S;Bussler H;Scrivens M;Jonason A;Mallow C;Doherty M;Paris M;Smith ES;Zauderer M
通讯作者：
Zauderer M
影响因子：
3.7
作者：
Gold L;Ayers D;Bertino J;Bock C;Bock A;Brody EN;Carter J;Dalby AB;Eaton BE;Fitzwater T;Flather D;Forbes A;Foreman T;Fowler C;Gawande B;Goss M;Gunn M;Gupta S;Halladay D;Heil J;Heilig J;Hicke B;Husar G;Janjic N;Jarvis T;Jennings S;Katilius E;Keeney TR;Kim N;Koch TH;Kraemer S;Kroiss L;Le N;Levine D;Lindsey W;Lollo B;Mayfield W;Mehan M;Mehler R;Nelson SK;Nelson M;Nieuwlandt D;Nikrad M;Ochsner U;Ostroff RM;Otis M;Parker T;Pietrasiewicz S;Resnicow DI;Rohloff J;Sanders G;Sattin S;Schneider D;Singer B;Stanton M;Sterkel A;Stewart A;Stratford S;Vaught JD;Vrkljan M;Walker JJ;Watrobka M;Waugh S;Weiss A;Wilcox SK;Wolfson A;Wolk SK;Zhang C;Zichi D
通讯作者：
Zichi D
DOI：
10.1073/pnas.2105822118
发表时间：
2021-10-12
影响因子：
11.1
作者：
Aoki T;Chong LC;Takata K;Milne K;Marshall A;Chavez EA;Miyata-Takata T;Ben-Neriah S;Unrau D;Telenius A;Boyle M;Weng AP;Savage KJ;Scott DW;Farinha P;Shah SP;Nelson BH;Steidl C
通讯作者：
Steidl C
影响因子：
7.5
作者：
Pierson, Sheila K.;Shenoy, Sushila;Fajgenbaum, David C.
通讯作者：
Fajgenbaum, David C.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y