Plasma Cytokine Profiling to Predict Steroid Resistance in Pediatric Nephrotic Syndrome.
Plasma Cytokine Profiling to Predict Steroid Resistance in Pediatric Nephrotic Syndrome.
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血浆细胞因子谱预测儿童肾病综合征的类固醇抵抗。
DOI：
10.1016/j.ekir.2020.12.027
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发表时间：
2021-03
影响因子：
6
通讯作者：
Pediatric Nephrology Research Consortium
中科院分区：
文献类型：
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作者：
Agrawal S;Brier ME;Kerlin BA;Smoyer WE;Pediatric Nephrology Research Consortium
糖皮质激素（GCs）是肾病综合征（NS）的主要治疗方法，尽管约10%至20%的儿童会出现类固醇抵抗性NS （SRNS）。不幸的是，目前还没有有效的生物标志物能够在疾病初始表现时预测SRNS。我们假设血浆细胞因子面板可以在疾病出现时预测SRNS，并确定调节SRNS发病机制的潜在途径。收集了26例类固醇敏感性NS （SSNS）患儿和14例SRNS患儿的配对血浆样本，这些患儿在出现NS时和GC治疗约7周后（临床确定SSNS vs SRNS）。用27种细胞因子进行血浆细胞因子分析。我们发现13种细胞因子在预处理SSNS和SRNS样品中显著不同。统计建模鉴定出一个细胞因子面板（白细胞介素[IL]-7、IL-9、单核细胞化学引诱蛋白-1 [MCP-1]），能够在疾病表现时区分SSNS和SRNS（受试者工作特征[ROC]值= 0.846；敏感性= 0.643；特异性= 0.846）。此外，GC治疗导致SSNS和SRNS患者血浆干扰素-γ (IFN-γ)、肿瘤坏死因子-α (TNF-α)、IL-7、IL-13和IL-5显著降低。这些研究表明，NS初始GC处理降低了CD4+ TH1细胞和TH2细胞以及CD8+ T细胞分泌的血浆细胞因子。重要的是，一组3种细胞因子（IL-7， IL-9和MCP-1）能够在疾病出现时GC治疗之前预测SRNS。虽然这些发现将受益于更大队列的验证，但在疾病出现时识别SRNS的能力可以通过避免不必要的gc诱导毒性和更早地过渡到更有效的替代治疗而极大地造福患者。
Glucocorticoids (GCs) are the primary treatment for nephrotic syndrome (NS), although ∼10% to 20% of children develop steroid-resistant NS (SRNS). Unfortunately, there are no validated biomarkers able to predict SRNS at initial disease presentation. We hypothesized that a plasma cytokine panel could predict SRNS at disease presentation, and identify potential pathways regulating SRNS pathogenesis. Paired plasma samples were collected from 26 children with steroid-sensitive NS (SSNS) and 14 with SRNS at NS presentation and after ∼7 weeks of GC therapy, when SSNS versus SRNS was clinically determined. Plasma cytokine profiling was performed with a panel of 27 cytokines. We identified 13 cytokines significantly different in Pretreatment SSNS versus SRNS samples. Statistical modeling identified a cytokine panel (interleukin [IL]-7, IL-9, monocyte chemoattractant protein–1 [MCP-1]) able to discriminate between SSNS and SRNS at disease presentation (receiver operating characteristic [ROC] value = 0.846; sensitivity = 0.643; specificity = 0.846). Furthermore, GC treatment resulted in significant decreases in plasma interferon-γ (IFN-γ), tumor necrosis factor–α (TNF-α), IL-7, IL-13, and IL-5 in both SSNS and SRNS patients. These studies suggest that initial GC treatment of NS reduces the plasma cytokines secreted by both CD4+ TH1 cells and TH2 cells, as well as CD8+ T cells. Importantly, a panel of 3 cytokines (IL-7, IL-9, and MCP-1) was able to predict SRNS prior to GC treatment at disease presentation. Although these findings will benefit from validation in a larger cohort, the ability to identify SRNS at disease presentation could greatly benefit patients by enabling both avoidance of unnecessary GC-induced toxicity and earlier transition to more effective alternative treatments.
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DOI：
10.1177/0300060516652762
发表时间：
2017-06
期刊：
The Journal of international medical research
影响因子：
--
作者：
Kang HG;Seo H;Lim JH;Kim JI;Han KH;Park HW;Koo JW;Kim KH;Kim JH;Cheong HI;Ha IS
通讯作者：
Ha IS
影响因子：
2.6
作者：
Decker, Marie-Luise;Grobusch, Martin P.;Ritz, Nicole
通讯作者：
Ritz, Nicole
影响因子：
3
作者：
Besbas, Nesrin;Kalyoncu, Mukaddes;Ozaltin, Fatih
通讯作者：
Ozaltin, Fatih
影响因子：
3.8
作者：
Bennett MR;Pleasant L;Haffner C;Ma Q;Haffey WD;Ying J;Wagner M;Greis KD;Devarajan P
通讯作者：
Devarajan P
影响因子：
19.6
作者：
通讯作者：
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