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Bridging a diagnostic Kawasaki disease classifier from a microarray platform to a qRT-PCR assay

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Title: Bridging a diagnostic Kawasaki disease classifier from a microarray platform to a qRT-PCR assay
Authors: Kuiper, R
Wright, VJ
Habgood-Coote, D
Shimizu, C
Huigh, D
Tremoulet, AH
Van Keulen, D
Hoggart, CJ
Rodriguez-Manzano, J
Herberg, JA
Kaforou, M
Tempel, D
Burns, JC
Levin, M
Item Type: Journal Article
Abstract: BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis that mainly affects children under 5 years of age. Up to 30% of patients develop coronary artery abnormalities, which are reduced with early treatment. Timely diagnosis of KD is challenging but may become more straightforward with the recent discovery of a whole-blood host response classifier that discriminates KD patients from patients with other febrile conditions. Here, we bridged this microarray-based classifier to a clinically applicable quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay: the Kawasaki Disease Gene Expression Profiling (KiDs-GEP) classifier. METHODS: We designed and optimized a qRT-PCR assay and applied it to a subset of samples previously used for the classifier discovery to reweight the original classifier. RESULTS: The performance of the KiDs-GEP classifier was comparable to the original classifier with a cross-validated area under the ROC curve of 0.964 [95% CI: 0.924-1.00] vs 0.992 [95% CI: 0.978-1.00], respectively. Both classifiers demonstrated similar trends over various disease conditions, with the clearest distinction between individuals diagnosed with KD vs viral infections. CONCLUSION: We successfully bridged the microarray-based classifier into the KiDs-GEP classifier, a more rapid and more cost-efficient qRT-PCR assay, bringing a diagnostic test for KD closer to the hospital clinical laboratory. IMPACT: A diagnostic test is needed for Kawasaki disease and is currently not available. We describe the development of a One-Step multiplex qRT-PCR assay and the subsequent modification (i.e., bridging) of the microarray-based host response classifier previously described by Wright et al. The bridged KiDs-GEP classifier performs well in discriminating Kawasaki disease patients from febrile controls. This host response clinical test for Kawasaki disease can be adapted to the hospital clinical laboratory.
Issue Date: 22-Jun-2022
Date of Acceptance: 25-May-2022
URI: http://hdl.handle.net/10044/1/98037
DOI: 10.1038/s41390-022-02148-y
ISSN: 0031-3998
Publisher: Springer Nature [academic journals on nature.com]
Journal / Book Title: Pediatric Research
Copyright Statement: © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: Wellcome Trust
Medical Research Foundation
Funder's Grant Number: 206508/Z/17/Z
Keywords: 1114 Paediatrics and Reproductive Medicine
1117 Public Health and Health Services
Publication Status: Published online
Conference Place: United States
Open Access location: https://www.nature.com/articles/s41390-022-02148-y
Online Publication Date: 2022-06-22
Appears in Collections:Department of Infectious Diseases

This item is licensed under a Creative Commons License Creative Commons