Diagnosis of Multisystem Inflammatory Syndrome in Children by a Whole-Blood Transcriptional Signature

被引：11

作者：

Jackson, Heather R. ^{[1
,2
]}

Miglietta, Luca ^{[1
,3
]}

Habgood-Coote, Dominic ^{[1
,2
]}

D'Souza, Giselle ^{[1
,2
]}

Shah, Priyen ^{[1
,2
]}

Nichols, Samuel ^{[1
,2
]}

Vito, Ortensia ^{[1
,2
]}

Powell, Oliver ^{[1
,2
]}

Davidson, Maisey Salina ^{[1
,2
]}

Shimizu, Chisato ^{[4
,5
]}

Agyeman, Philipp K. A. ^{[6
]}

Beudeker, Coco R. ^{[7
]}

Brengel-Pesce, Karen ^{[8
]}

Carrol, Enitan D. ^{[9
]}

Carter, Michael J. ^{[10
,11
]}

De, Tisham ^{[1
,2
]}

Eleftheriou, Irini ^{[12
]}

Emonts, Marieke ^{[13
,14
,15
,16
]}

Epalza, Cristina ^{[17
]}

Georgiou, Pantelis ^{[3
]}

De Groot, Ronald ^{[18
,19
]}

Fidler, Katy ^{[20
]}

Fink, Colin ^{[21
]}

van Keulen, Danielle ^{[22
]}

Kuijpers, Taco ^{[23
,24
,25
]}

Moll, Henriette ^{[26
]}

Papatheodorou, Irene ^{[27
]}

Paulus, Stephane ^{[28
,29
]}

Pokorn, Marko ^{[30
,31
]}

Pollard, Andrew J. ^{[28
,29
]}

Rivero-Calle, Irene ^{[32
,33
,34
,35
]}

Rojo, Pablo ^{[17
]}

Secka, Fatou ^{[36
]}

Schlapbach, Luregn J. ^{[37
,38
,39
]}

Tremoulet, Adriana H. ^{[4
,5
]}

Tsolia, Maria ^{[12
]}

Usuf, Effua ^{[36
]}

Van der Flier, Michiel ^{[7
]}

Von Both, Ulrich ^{[40
]}

Vermont, Clementien ^{[41
]}

Yeung, Shunmay ^{[42
]}

Zavadska, Dace ^{[43
]}

Zenz, Werner ^{[44
]}

Coin, Lachlan J. M. ^{[45
]}

Cunnington, Aubrey ^{[1
,2
]}

Burns, Jane C. ^{[4
,5
]}

Wright, Victoria ^{[1
,2
]}

Martinon-Torres, Federico ^{[32
,33
,34
,35
]}

Herberg, Jethro A. ^{[1
,2
]}

Rodriguez-Manzano, Jesus ^{[1
]}

机构：

[1] Imperial Coll London, Fac Med, Dept Infect Dis, London, England

[2] Imperial Coll London, Ctr Paediat & Child Hlth, London SW7 2AZ, England

[3] Imperial Coll London, Fac Engn, Dept Elect & Elect Engn, London, England

[4] Rady Childrens Hosp, Dept Pediat, La Jolla, CA USA

[5] Univ Calif San Diego, La Jolla, CA USA

[6] Univ Bern, Bern Univ Hosp, Dept Pediat, Inselspital, Bern, Switzerland

[7] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Dept Paediat Infect Dis & Immunol, Utrecht, Netherlands

[8] Lyon Sud Hosp, Joint Res Unit Hosp Civils Lyon bioMerieux, Pierre Benite, France

[9] Univ Liverpool, Dept Clin Infect Microbiol & Immunol, Inst Infect Vet & Ecol Sci, Liverpool, Merseyside, England

[10] Guys & St Thomas NHS Fdn Trust, Evelina London Childrens Hosp, Paediat Intens Care, London, England

[11] Kings Coll London, St Thomas Hosp, Sch Life Course Sci, Dept Women & Childrens Hlth, London, England

[12] Natl & Kapodistrian Univ Athens NKUA, P&A Kyriakou Childrens Hosp, Sch Med, Dept Paediat 2, Athens, Greece

[13] Newcastle Univ, Translat & Clin Res Inst, Newcastle Upon Tyne, Tyne & Wear, England

[14] Newcastle upon Tyne Hosp Fdn Trust, Great North Childrens Hosp, Paediat Infect Dis & Immunol Dept, Newcastle Upon Tyne, Tyne & Wear, England

[15] Newcastle upon Tyne Hosp NHS Trust, NIHR Newcastle Biomed Res Ctr, Newcastle Upon Tyne, Tyne & Wear, England

[16] Newcastle Univ, Newcastle Upon Tyne, Tyne & Wear, England

[17] Hosp Doce Octubre, Pediat Dept, Pediat Infect Dis Unit, Madrid, Spain

[18] Radboudumc, Dept Pediat, Div Pediat Infect Dis & Immunol, Nijmegen, Netherlands

[19] Radboudumc, Radboud Inst Mol Life Sci, Lab Infect Dis, Nijmegen, Netherlands

[20] Univ Hosp Sussex, Royal Alexandra Childrens Hosp, Acad Dept Paediat, Brighton, E Sussex, England

[21] Univ Warwick, Micropathol Ltd, Warwick, England

[22] SkylineDx, Rotterdam, Netherlands

[23] Univ Amsterdam, Emma Childrens Hosp, Dept Pediat Immunol Rheumatol & Infect Dis, Med Ctr, Amsterdam, Netherlands

[24] Univ Amsterdam, Dept Blood Cell Res, Sanquin Res, Med Ctr, Amsterdam, Netherlands

[25] Univ Amsterdam, Landsteiner Lab, Med Ctr, Amsterdam, Netherlands

[26] Erasmus MC Sophia Childrens Hosp, Dept Pediat, Rotterdam, Netherlands

[27] EMBL European Bioinformat Inst EMBL EBI, Gene Express Team, European Mol Biol Lab, Cambridge, England

[28] Univ Oxford, Dept Paediat, Oxford Vaccine Grp, Oxford, England

[29] NIHR Oxford Biomed Res Ctr, Oxford, England

[30] Univ Med Ctr Ljubljana, Div Pediat, Ljubljana, Slovenia

[31] Univ Ljubljana, Med Fac, Ljubljana, Slovenia

[32] Translat Pediat & Infect Dis Sect, Pediat Dept, Santiago De Compostela, Spain

[33] Univ Santiago de Compostela USC, Inst Invest Sanitaria Santiago IDIS, Genet Vaccines Infect Dis & Pediat Res Grp GENVIP, Santiago De Compostela, Spain

[34] Univ Santiago de Compostela, Dept Anat Patolox & Ciencias Forenses, Unidade Xenet, Inst Ciencias Forenses,Fac Med, Galicia, Spain

[35] Hosp Clin Univ Santiago SERGAS, Inst Invest Sanitarias IDIS, GenPoB Res Grp, Galicia, Spain

[36] Gambia London Sch Hyg & Trop Med, Med Res Council Unit, Banjul, Gambia

[37] Univ Childrens Hosp Zurich, Dept Intens Care & Neonatol, Zurich, Switzerland

[38] Univ Childrens Hosp Zurich, Childrens Res Ctr, Zurich, Switzerland

[39] Univ Queensland, Child Hlth Res Ctr, Brisbane, Qld, Australia

[40] Ludwig Maximilians Univ Munchen, Dr von Hauner Childrens Hosp, Dept Pediat, Div Pediat Infect Dis,Univ Hosp, Munich, Germany

[41] Erasmus MC Sophia Childrens Hosp, Dept Paediat Infect Dis & Immunol, Rotterdam, Netherlands

[42] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Clin Res Dept, London, England

[43] Childrens Clin Univ Hosp, Dept Pediat, Riga, Latvia

[44] Med Univ Graz, Univ Clin Paediat & Adolescent Med, Dept Gen Paediat, Graz, Austria

[45] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Vic, Australia

来源：

JOURNAL OF THE PEDIATRIC INFECTIOUS DISEASES SOCIETY | 2023年 / 12卷 / 06期

基金：

美国国家卫生研究院; 英国惠康基金;

关键词：

COVID-19; diagnostic signature; host diagnostics; host response; MIS-C; pediatric infectious diseases; rapid diagnostics; transcriptomics; DISEASE; SARS-COV-2; COVID-19; INFECTIONS; EXPRESSION; DISCOVERY; SEVERITY; SHOCK;

D O I：

10.1093/jpids/piad035

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Background 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.Methods 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).Results 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.Conclusions 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.

引用

页码：322 / 331

页数：10

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