Academic Journal
Diagnosis of multisystem inflammatory syndrome in children by a whole-blood transcriptional signature
| العنوان: | Diagnosis of multisystem inflammatory syndrome in children by a whole-blood transcriptional signature |
|---|---|
| المؤلفون: | Jackson, HR, Miglietta, L, Habgood-Coote, D, D'Souza, G, Shah, P, Nichols, S, Vito, O, Powell, O, Davidson, MS, Shimizu, C, Agyeman, PKA, Beudeker, CR, Brengel-Pesce, K, Carrol, ED, Carter, MJ, De, T, Eleftheriou, I, Emonts, M, Epalza, C, Georgiou, P, De Groot, R, Fidler, K, Fink, C, van Keulen, D, Kuijpers, T, Moll, H, Papatheodorou, I, Paulus, S, Pokorn, M, Pollard, AJ, Rivero-Calle, I, Rojo, P, Secka, F, Schlapbach, LJ, Tremoulet, AH, Tsolia, M, Usuf, E, Van Der Flier, M, Von Both, U, Vermont, C, Yeung, S, Zavadska, D, Zenz, W, Coin, LJM, Cunnington, A, Burns, JC, Wright, V, Martinon-Torres, F, Herberg, JA, Rodriguez-Manzano, J, Kaforou, M, Levin, M |
| المساهمون: | EUCLIDS, PERFORM, and DIAMONDS Consortia |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2023 |
| المجموعة: | Oxford University Research Archive (ORA) |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | https://ora.ox.ac.uk/objects/uuid:acee3dd1-0f80-4489-bcbb-007e2506ff84; https://doi.org/10.1093/jpids/piad035 |
| DOI: | 10.1093/jpids/piad035 |
| الاتاحة: | https://doi.org/10.1093/jpids/piad035 https://ora.ox.ac.uk/objects/uuid:acee3dd1-0f80-4489-bcbb-007e2506ff84 |
| Rights: | info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| رقم الانضمام: | edsbas.8D02FBEA |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/jpids/piad035 |
|---|