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

共 50 条

[31] Whole-blood viscosity and metabolic syndrome
Gyawali, Prajwal
Richards, Ross S.
Nwose, Ezekiel Uba
Bwititi, Phillip T.
CLINICAL LIPIDOLOGY, 2012, 7 (06) : 709 - 719
[32] HEXACHLOROBENZENE CONTENT IN WHOLE-BLOOD OF CHILDREN
RICHTER, E
SCHMID, A
ARCHIVES OF TOXICOLOGY, 1976, 35 (02) : 141 - 147
[33] Diagnosis and Acute Management of COVID-19 and Multisystem Inflammatory Syndrome in Children
Kortz, Teresa B.
Connolly, Emilia
Cohen, C. Lee
Cook, Rebecca E.
Jonas, Jennifer A.
Lipnick, Michael S.
Kissoon, Niranjan
PEDIATRIC EMERGENCY CARE, 2021, 37 (10) : 519 - 525
[34] The challenges of multisystem inflammatory syndrome diagnosis and treatment
Kiaunyte, Saule
Sileikiene, Rima
SIGNA VITAE, 2024, 20 (02) : 105 - 109
[35] Diagnosis and treatment of paediatric inflammatory multisystem syndrome
Constantin Tamas
Andrasi Noemi
Ponyi Andrea
Goschler Adam
Ablonczy Laszlo
Kincs Judit
Csoka Monika
Egyed Balint
Horvath Zsuzsanna
Kalocsai Krisztina
Kaposzta Rita
Kardics Kinga
Kemeny Viktoria
Mosdosi Bernadett
Pek Tamas
Szabo Zsofia
Toth Attila
Tory Kalman
Tolgyesi Andrea
Onozo Beata
Vago Hajnalka
Vilmanyi Csaba
Weiser, Peter
Szekanecz Zoltan
Kovacs Gabor
Szabo Attila
ORVOSI HETILAP, 2021, 162 (17) : 652 - 667
[36] Is multisystem inflammatory syndrome in children on the Kawasaki syndrome spectrum?
Yeung, Rae S. M.
Ferguson, Polly J.
JOURNAL OF CLINICAL INVESTIGATION, 2020, 130 (11): : 5681 - 5684
[37] Therapy for Multisystem Inflammatory Syndrome in Children REPLY
McArdle, Andrew J.
Cunnington, Aubrey J.
Levin, Michael
NEW ENGLAND JOURNAL OF MEDICINE, 2021, 385 (13):
[38] Multisystem Inflammatory Syndrome in New Zealand Children
Taylor, Amanda
Duncanson, Mavis
Mitchelson, Bryan
Nuthall, Gabrielle
Voss, Lesley
Walls, Tony
Dalziel, Stuart R.
Ostring, Genevieve
Best, Emma J.
PEDIATRIC INFECTIOUS DISEASE JOURNAL, 2023, 42 (07) : E232 - E234
[39] Multisystem Inflammatory Syndrome in US Children and Adolescents
Young, Marielle C.
Pistiner, Michael
PEDIATRICS, 2021, 148 : S74 - S75
[40] Hyponatremia in Patients With Multisystem Inflammatory Syndrome in Children
Mills, Tatyana
Trivedi, Aditi
Tremoulet, Adriana H.
Hershey, Daniel
Burns, Jane C.
PEDIATRIC INFECTIOUS DISEASE JOURNAL, 2021, 40 (09) : E344 - E346

← 1 2 3 4 5 →