Plasma cell-free RNA signatures of inflammatory syndromes in children

Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), viral infections, and bacterial infections. We developed machine learning models based on these cfRNA profiles, which effectively differentiated KD from MIS-C-two conditions presenting with overlapping symptoms-with high performance [test area under the curve = 0.98]. We further extended this methodology into a multiclass machine learning framework that achieved 80% accuracy in distinguishing among KD, MIS-C, viral, and bacterial infections. We further demonstrated that cfRNA profiles can be used to quantify injury to specific tissues and organs, including the liver, heart, endothelium, nervous system, and the upper respiratory tract. Overall, this study identified cfRNA as a versatile analyte for the differential diagnosis and characterization of a wide range of pediatric inflammatory syndromes.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2024-09-06
DOI
https://doi.org/10.1073/pnas.2403897121
Citations
17
Primary Topic
Extracellular vesicles in disease
Type
article
Field-Weighted Citation Impact
3.97

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article

Plasma cell-free RNA signatures of inflammatory syndromes in children

J. Joelle Donofrio-Ödmann, Joan Sesing Lenz, Paul Ishimine, Laura D’Addese et al.
17 citations
Proceedings of the National Academy of Sciences
Extracellular vesicles in disease
3.97
article

Plasma cell-free RNA signatures of inflammatory syndromes in children

J. Joelle Donofrio-Ödmann, Joan Sesing Lenz, Paul Ishimine, Laura D’Addese, Iwijn De Vlaminck, Tatyana Vayngortin, Alicia Sotomayor-González, Lerraughn Morgan, Adriana H. Tremoulet, Meagan E. Williams, Lukas Austin-Page, Charles Y. Chiu, Margaret Nguyen, John T. Kanegaye, Conor Loy, Margalit Rosenkranz, Atim Ekpenyong, Miriam Oseguera, Michelle Sykes, David J. Gutglass, Stacey Ulrich, Amy Bryl, Elise Zimmerman, J. Sidney Ang, Jenny Nguyen, Hao Wang, Jane C. Burns, Roberta L. DeBiasi, Meghan Delaney, Andrew Bliss, Christina A. Rostad, Kristy Schwartz, Venice Servellita, Chisato Shimizu, Will Suslovic, Jihoon Kim, My-Linh T. Nguyen, Joseph Bochini, Maria Pilar Gutierrez, S. Herskovitz, Hui‐Mien Hsiao, Michael Gardiner, Jong-Ha Choi, E. H. Belcher
article en
17 citations

Abstract

Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), viral infections, and bacterial infections. We developed machine learning models based on these cfRNA profiles, which effectively differentiated KD from MIS-C-two conditions presenting with overlapping symptoms-with high performance [test area under the curve = 0.98]. We further extended this methodology into a multiclass machine learning framework that achieved 80% accuracy in distinguishing among KD, MIS-C, viral, and bacterial infections. We further demonstrated that cfRNA profiles can be used to quantify injury to specific tissues and organs, including the liver, heart, endothelium, nervous system, and the upper respiratory tract. Overall, this study identified cfRNA as a versatile analyte for the differential diagnosis and characterization of a wide range of pediatric inflammatory syndromes.

Proceedings of the National Academy of SciencesVol. 121(37)
Children's National (US), Emory University (US), University of California, San Francisco (US), George Washington University (US), Cornell University (US), Yale University (US), University of California San Diego (US), Rady Children's Hospital-San Diego (US), Chan Zuckerberg Initiative (United States) (US), Children's Healthcare of Atlanta (US)
Abbott Laboratories, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Good health and well-being
Openalex Percentile: Top 5%
Extracellular vesicles in disease
3.97
DOIOpen Access PDFOpenAlex
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