{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T07:37:49Z","timestamp":1793086669341,"version":"4.5.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013342","name":"NIHR Imperial Biomedical Research Centre","doi-asserted-by":"publisher","award":["206508\/Z\/17\/Z"],"award-info":[{"award-number":["206508\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/501100013342","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013342","name":"NIHR Imperial Biomedical Research Centre","doi-asserted-by":"publisher","award":["MRF-160-0008-ELP-KAFO-C0801"],"award-info":[{"award-number":["MRF-160-0008-ELP-KAFO-C0801"]}],"id":[{"id":"10.13039\/501100013342","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215214\/Z\/19\/Z"],"award-info":[{"award-number":["215214\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["R61HD105590-01"],"award-info":[{"award-number":["R61HD105590-01"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["WDPI_G28062"],"award-info":[{"award-number":["WDPI_G28062"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["WDPI_P89720"],"award-info":[{"award-number":["WDPI_P89720"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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%\u201398.9%) 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%\u201397.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jpids\/piad035","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T13:03:45Z","timestamp":1685538225000},"page":"322-331","source":"Crossref","is-referenced-by-count":24,"title":["Diagnosis of Multisystem Inflammatory Syndrome in Children by a Whole-Blood Transcriptional Signature"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1054-9983","authenticated-orcid":false,"given":"Heather R","family":"Jackson","sequence":"first","affiliation":[{"name":"Department of Infectious Disease, Faculty of Medicine, Imperial College London , London , UK"},{"name":"Centre for Paediatrics and Child Health, Imperial College London , London, SW7 2AZ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Miglietta","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Faculty of Medicine, Imperial College London , London , UK"},{"name":"Department of Electrical and Electronic Engineering, Faculty of Engineering, Imperial College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic","family":"Habgood-Coote","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Faculty of Medicine, Imperial College London , London , UK"},{"name":"Centre for Paediatrics and Child Health, Imperial College London , London, SW7 2AZ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giselle","family":"D\u2019Souza","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Faculty of Medicine, Imperial College London , London , UK"},{"name":"Centre for Paediatrics and Child Health, Imperial College London , London, SW7 2AZ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyen","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Faculty of Medicine, Imperial College London , London , UK"},{"name":"Centre for Paediatrics and Child Health, Imperial College London , London, SW7 2AZ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Nichols","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Faculty of Medicine, Imperial College London , London , UK"},{"name":"Centre for Paediatrics and Child Health, Imperial College London , London, SW7 2AZ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ortensia","family":"Vito","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Faculty of Medicine, Imperial College London , London , UK"},{"name":"Centre for Paediatrics and Child Health, Imperial College London , London, SW7 2AZ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Powell","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Faculty of Medicine, Imperial College London , London , UK"},{"name":"Centre for Paediatrics and Child Health, Imperial College London , London, SW7 2AZ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maisey Salina","family":"Davidson","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Faculty of Medicine, Imperial College London , London , UK"},{"name":"Centre for Paediatrics and Child Health, Imperial College London , London, SW7 2AZ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisato","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Rady Children\u2019s Hospital and University of California San Diego , La Jolla, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8339-5444","authenticated-orcid":false,"given":"Philipp K A","family":"Agyeman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern , Bern , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coco R","family":"Beudeker","sequence":"additional","affiliation":[{"name":"Department of Paediatric Infectious Diseases and Immunology, Wilhelmina Children\u2019s Hospital, University Medical Centre Utrecht , Utrecht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Brengel-Pesce","sequence":"additional","affiliation":[{"name":"Joint Research Unit Hospices Civils de Lyon-bioM\u00e9rieux, Lyon Sud Hospital , Pierre-B\u00e9nite , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enitan D","family":"Carrol","sequence":"additional","affiliation":[{"name":"Department of Clinical Infection Microbiology and Immunology, University of Liverpool Institute of Infection, Veterinary and Ecological Sciences , Liverpool , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Carter","sequence":"additional","affiliation":[{"name":"Paediatric Intensive Care, Evelina London Children\u2019s Hospital, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust , London , UK"},{"name":"Department of Women and Children\u2019s Health, School of Life Course Sciences, King\u2019s College London, St Thomas\u2019 Hospital , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tisham","family":"De","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Faculty of Medicine, Imperial College London , London , UK"},{"name":"Centre for Paediatrics and Child Health, Imperial College London , London, SW7 2AZ , 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Kyriakou Children\u2019s Hospital , Athens , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke","family":"Emonts","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University , Newcastle upon Tyne , UK"},{"name":"Paediatric Infectious Diseases and Immunology Department, Newcastle upon Tyne Hospitals Foundation Trust, Great North Children\u2019s Hospital , Newcastle upon Tyne , UK"},{"name":"NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust and Newcastle University , Newcastle upon Tyne , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6929-4903","authenticated-orcid":false,"given":"Cristina","family":"Epalza","sequence":"additional","affiliation":[{"name":"Pediatric Infectious Diseases Unit, Pediatric Department, Hospital Doce de Octubre , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pantelis","family":"Georgiou","sequence":"additional","affiliation":[{"name":"Department of Electrical and Electronic Engineering, Faculty of Engineering, Imperial College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"De Groot","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology and Laboratory of Infectious Diseases, Radboud Institute of Molecular Life Sciences, Radboudumc , Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katy","family":"Fidler","sequence":"additional","affiliation":[{"name":"Academic Department of Paediatrics, Royal Alexandra Children\u2019s Hospital, University Hospitals Sussex , Brighton , 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Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9304-3322","authenticated-orcid":false,"given":"Henriette","family":"Moll","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Erasmus MC Sophia Children\u2019s Hospital , Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7270-5470","authenticated-orcid":false,"given":"Irene","family":"Papatheodorou","sequence":"additional","affiliation":[{"name":"Gene Expression Team, European Molecular Biology Laboratory, EMBL-European Bioinformatics Institute (EMBL-EBI) , Hinxton, Cambridge , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Paulus","sequence":"additional","affiliation":[{"name":"Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre , Oxford , 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(USC) , Santiago de Compostela , Spain"},{"name":"Unidade de Xen\u00e9tica, Departamento de Anatom\u00eda Patol\u00f3xica e Ciencias Forenses, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela , Galicia , Spain"},{"name":"GenPoB Research Group, Instituto de Investigaciones Sanitarias (IDIS), Hospital Cl\u00ednico Universitario de Santiago (SERGAS) , Galicia , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Rojo","sequence":"additional","affiliation":[{"name":"Pediatric Infectious Diseases Unit, Pediatric Department, Hospital Doce de Octubre , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatou","family":"Secka","sequence":"additional","affiliation":[{"name":"Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine , Banjul , Gambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luregn J","family":"Schlapbach","sequence":"additional","affiliation":[{"name":"Department of Intensive Care and Neonatology, and Children\u2019s Research Center, University Children`s Hospital Zurich , Zurich , Switzerland"},{"name":"Child Health Research Centre, The University of Queensland , Brisbane, Queensland , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana H","family":"Tremoulet","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Rady Children\u2019s Hospital and University of California San Diego , La Jolla, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Tsolia","sequence":"additional","affiliation":[{"name":"Second Department of Paediatrics, National and Kapodistrian University of Athens (NKUA), School of Medicine, P. and A. Kyriakou Children\u2019s Hospital , Athens , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Effua","family":"Usuf","sequence":"additional","affiliation":[{"name":"Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine , Banjul , Gambia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel","family":"Van Der Flier","sequence":"additional","affiliation":[{"name":"Department of Paediatric Infectious Diseases and Immunology, Wilhelmina Children\u2019s Hospital, University Medical Centre Utrecht , Utrecht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8411-1071","authenticated-orcid":false,"given":"Ulrich","family":"Von Both","sequence":"additional","affiliation":[{"name":"Division of Pediatric Infectious Diseases, Department of Pediatrics, Dr von Hauner Children\u2019s Hospital, University Hospital, LMU Munich , Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clementien","family":"Vermont","sequence":"additional","affiliation":[{"name":"Department of Paediatric Infectious Diseases and Immunology, Erasmus MC Sophia Children\u2019s Hospital , Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0997-0850","authenticated-orcid":false,"given":"Shunmay","family":"Yeung","sequence":"additional","affiliation":[{"name":"Clinical Research Department, Faculty of Infectious and Tropical Disease, London School of Hygiene and Tropical Medicine , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dace","family":"Zavadska","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Clinical University Hospital , R\u012bga , 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UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane C","family":"Burns","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Rady Children\u2019s Hospital and University of California San Diego , La Jolla, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Faculty of Medicine, Imperial College London , London , UK"},{"name":"Centre for Paediatrics and Child Health, Imperial College London , London, SW7 2AZ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Martinon-Torres","sequence":"additional","affiliation":[{"name":"Pediatrics Department, Translational Pediatrics and Infectious Diseases Section , Santiago de Compostela , Spain"},{"name":"Genetics\u2013Vaccines\u2013Infectious Diseases and Pediatrics Research Group GENVIP, Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS), Universidade de Santiago de Compostela (USC) , Santiago de Compostela , Spain"},{"name":"Unidade de Xen\u00e9tica, Departamento de Anatom\u00eda Patol\u00f3xica e Ciencias Forenses, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela , Galicia , Spain"},{"name":"GenPoB Research Group, Instituto de Investigaciones Sanitarias (IDIS), Hospital Cl\u00ednico Universitario de Santiago (SERGAS) , Galicia , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6941-6491","authenticated-orcid":false,"given":"Jethro A","family":"Herberg","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Faculty of Medicine, Imperial College London , London , UK"},{"name":"Centre for Paediatrics and Child Health, Imperial College London , London, SW7 2AZ , 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