Diagnosis of Multisystem Inflammatory Syndrome in Children by a Whole-Blood Transcriptional Signature.
Diagnosis of Multisystem Inflammatory Syndrome in Children by a Whole-Blood Transcriptional Signature.
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DOI：
10.1093/jpids/piad035
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发表时间：
2023-06-30
影响因子：
3.2
通讯作者：
中科院分区：
文献类型：
--
作者：
目的：确定一种诊断血液转录特征，以区分儿童多系统炎症综合征(MIS-C)和川崎病(KD)、细菌感染和病毒感染。在2020年4月至2021年4月期间向英国和欧盟的参与医院提供管理信息系统-C的儿童被预期招募。进行全血RNA测序，比较38例临床诊断为MIS-C的患儿与136例KD患儿、188例明确的细菌性感染患儿和138例DV感染患儿的转录本。鉴定了在MIS-C组和对照组之间显著差异表达(SDE)的基因。特征选择被用来识别与其他疾病最佳区分的基因，这些基因随后被转化为RT-qPCR分析，并在一个独立的验证集中进行评估，该验证集中包括MISC(n=37)、KD(n=19)、DB(n=56)、DV(n=43)和新冠肺炎(n=39)。在发现组中，有5696个基因是在MIS-C和联合对照疾病组之间的SDE。5个基因(HSPBAP1、VPS37C、TGFB1、MX2和TRBV11-2)被确定为潜在的MIS-C诊断标志物，在发现集中的AUC为96.8%(95%CI：94.6%-98.9%)，并被翻译成RT-qPCR检测。RT-qPCR5基因特征在独立验证集中的AUC为93.2%(95%CI：88.3%~97.7%)。利用5个基因的血液RNA表达特征，可以将MIS-C与KD、DB和DV组区分开来。签名中的少量基因，以及在发现和验证集上的良好表现，应该能够开发一种针对MIS-C的诊断测试。
To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections. Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138). Genes significantly differentially expressed (SDE) between MIS-C and comparator groups were identified. Feature selection was used to identify genes that optimally distinguish MIS-C from other diseases, which were subsequently translated into RT-qPCR assays and evaluated in an independent validation set comprising MIS-C (n = 37), KD (n = 19), DB (n = 56), DV (n = 43), and COVID-19 (n = 39). In the discovery set, 5696 genes were SDE between MIS-C and combined comparator disease groups. Five genes were identified as potential MIS-C diagnostic biomarkers (HSPBAP1, VPS37C, TGFB1, MX2, and TRBV11-2), achieving an AUC of 96.8% (95% CI: 94.6%–98.9%) in the discovery set, and were translated into RT-qPCR assays. The RT-qPCR 5-gene signature achieved an AUC of 93.2% (95% CI: 88.3%–97.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV. MIS-C can be distinguished from KD, DB, and DV groups using a 5-gene blood RNA expression signature. The small number of genes in the signature and good performance in both discovery and validation sets should enable the development of a diagnostic test for MIS-C.
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影响因子：
16.6
作者：
Ferreira-Gomes M;Kruglov A;Durek P;Heinrich F;Tizian C;Heinz GA;Pascual-Reguant A;Du W;Mothes R;Fan C;Frischbutter S;Habenicht K;Budzinski L;Ninnemann J;Jani PK;Guerra GM;Lehmann K;Matz M;Ostendorf L;Heiberger L;Chang HD;Bauherr S;Maurer M;Schönrich G;Raftery M;Kallinich T;Mall MA;Angermair S;Treskatsch S;Dörner T;Corman VM;Diefenbach A;Volk HD;Elezkurtaj S;Winkler TH;Dong J;Hauser AE;Radbruch H;Witkowski M;Melchers F;Radbruch A;Mashreghi MF
通讯作者：
Mashreghi MF
影响因子：
36.4
作者：
Martinon-Torres, Federico;Salas, Antonio;Levin, Michael
通讯作者：
Levin, Michael
影响因子：
2.6
作者：
Nijman RG;Oostenbrink R;Moll HA;Casals-Pascual C;von Both U;Cunnington A;De T;Eleftheriou I;Emonts M;Fink C;van der Flier M;de Groot R;Kaforou M;Kohlmaier B;Kuijpers TW;Lim E;Maconochie IK;Paulus S;Martinon-Torres F;Pokorn M;Romaine ST;Calle IR;Schlapbach LJ;Smit FJ;Tsolia M;Usuf E;Wright VJ;Yeung S;Zavadska D;Zenz W;Levin M;Herberg JA;Carrol ED;PERFORM consortium (Personalized Risk assessment in febrile children to optimize Real-life Management across the European Union)
通讯作者：
PERFORM consortium (Personalized Risk assessment in febrile children to optimize Real-life Management across the European Union)
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
影响因子：
7.3
作者：
Gliddon HD;Kaforou M;Alikian M;Habgood-Coote D;Zhou C;Oni T;Anderson ST;Brent AJ;Crampin AC;Eley B;Heyderman R;Kern F;Langford PR;Ottenhoff THM;Hibberd ML;French N;Wright VJ;Dockrell HM;Coin LJ;Wilkinson RJ;Levin M
通讯作者：
Levin M