Plasma protein biomarkers distinguish Multisystem Inflammatory Syndrome in Children (MIS-C) from other pediatric infectious and inflammatory diseases

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Yeoh, Sophya, Estrada-Rivadeneyra, Diego ORCID: 0000-0003-2512-7131, Jackson, Heather ORCID: 0000-0002-1054-9983, Keren, Ilana, Galassini, Rachel ORCID: 0000-0002-1025-0367, Cooray, Samantha, Shah, Priyen ORCID: 0000-0001-9164-8862, Agyeman, Philipp ORCID: 0000-0002-8339-5444, Basmaci, Romain, Carrol, Enitan ORCID: 0000-0001-8357-7726 et al (show 26 more authors) , Emonts, Marieke, Fink, Colin, Kuijpers, Taco, Torres, Federico Martinon-, Mommert-Tripon, Marine, Paulus, Stephane, Pokorn, Marko, Rojo, Pablo, Romani, Lorenza, Schlapbach, Luregn ORCID: 0000-0003-2281-2598, Schweintzger, Nina, Shen, Ching-Fen, Tsolia, Maria, Usuf, Effua, Van der Flier, Michiel, Vermont, Clementien, Both, Ulrich Von, Yeung, Shunmay ORCID: 0000-0002-0997-0850, Zavadska, Dace, Coin, Lachlan, Cunnington, Aubrey ORCID: 0000-0002-1305-3529, Herberg, Jethro ORCID: 0000-0001-6941-6491, Levin, Michael ORCID: 0000-0003-2767-6919, Kaforou, Myrsini, Hamilton, Shea and UK KD Genetics Consortia (2023) Plasma protein biomarkers distinguish Multisystem Inflammatory Syndrome in Children (MIS-C) from other pediatric infectious and inflammatory diseases [Preprint]

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Abstract

<h4>ABSTRACT</h4> <h4>Background</h4> Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious hyperinflammatory complication following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The mechanisms underpinning the pathophysiology of MIS-C are poorly understood. Moreover, clinically distinguishing MIS-C from other childhood infectious and inflammatory conditions, such as Kawasaki Disease (KD) or severe bacterial and viral infections is challenging due to overlapping clinical and laboratory features. We aimed to determine a set of plasma protein biomarkers that could discriminate MIS-C from those other diseases. <h4>Methods</h4> Seven candidate protein biomarkers for MIS-C were selected based on literature and from whole blood RNA-Sequencing data from patients with MIS-C and other diseases. Plasma concentrations of ARG1, CCL20, CD163, CORIN, CXCL9, PCSK9 and ADAMTS2 were quantified in MIS-C (n=22), KD (n=23), definite bacterial (DB; n=28) and viral (DV, n=27) disease, and healthy controls (n=8). Logistic regression models were used to determine the discriminatory ability of individual proteins and protein combinations to identify MIS-C, and association with severity of illness. <h4>Results</h4> Plasma levels of CD163, CXCL9, and PCSK9 were significantly elevated in MIS-C with a combined AUC of 86% (95% CI: 76.8%-95.1%) for discriminating MIS-C from other childhood diseases. Lower ARG1 and CORIN plasma levels were significantly associated with severe MIS-C cases requiring oxygen, inotropes or with shock. <h4>Conclusion</h4> Our findings demonstrate the feasibility of a host protein biomarker signature for MIS-C and may provide new insight into its pathophysiology.

Item Type:	Preprint
Uncontrolled Keywords:	UK KD Genetics Consortia
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Infection, Vet & Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	10 Jun 2024 09:24
Last Modified:	07 Dec 2024 21:30
DOI:	10.1101/2023.07.28.23293197
Related Websites:	Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3182098
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