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Diagnosis of Multisystem Inflammatory Syndrome in Children by a Whole-Blood Transcriptional Signature.
- Source :
-
Journal of the Pediatric Infectious Diseases Society . Jun2023, Vol. 12 Issue 6, p322-331. 10p. - Publication Year :
- 2023
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HOSPITALS
*BIOMARKERS
*REVERSE transcriptase polymerase chain reaction
*MULTISYSTEM inflammatory syndrome
*COVID-19
*SEQUENCE analysis
*CONFIDENCE intervals
*RNA
*SYSTEMIC inflammatory response syndrome
*CONNECTIVE tissue diseases
*GENE expression profiling
*VIRUS diseases
*COVID-19 testing
*MUCOCUTANEOUS lymph node syndrome
*BACTERIAL diseases
*RECEIVER operating characteristic curves
*LONGITUDINAL method
*CHILDREN
Subjects
Details
- Language :
- English
- ISSN :
- 20487193
- Volume :
- 12
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Journal of the Pediatric Infectious Diseases Society
- Publication Type :
- Academic Journal
- Accession number :
- 164654251
- Full Text :
- https://doi.org/10.1093/jpids/piad035