Plasma protein biomarkers distinguish Multisystem Inflammatory Syndrome in Children (MIS-C) from other pediatric infectious and inflammatory diseases
Author:
Yeoh Sophya, Estrada-Rivadeneyra DiegoORCID, Jackson HeatherORCID, Keren Ilana, Galassini RachelORCID, Cooray SamanthaORCID, Shah PriyenORCID, Agyeman PhilippORCID, Basmaci RomainORCID, Carrol EnitanORCID, Emonts MariekeORCID, Fink ColinORCID, Kuijpers TacoORCID, Torres Federico Martinon-ORCID, Mommert-Tripon MarineORCID, Paulus StephaneORCID, Pokorn MarkoORCID, Rojo PabloORCID, Romani LorenzaORCID, Schlapbach LuregnORCID, Schweintzger NinaORCID, Shen Ching-FenORCID, Tsolia MariaORCID, Usuf EffuaORCID, Van der Flier MichielORCID, Vermont ClementienORCID, Both Ulrich VonORCID, Yeung ShunmayORCID, Zavadska DaceORCID, Coin LachlanORCID, Cunnington AubreyORCID, Herberg JethroORCID, Levin MichaelORCID, Kaforou MyrsiniORCID, Hamilton SheaORCID,
Abstract
ABSTRACTBackgroundMultisystem 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.MethodsSeven 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.ResultsPlasma 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.ConclusionOur findings demonstrate the feasibility of a host protein biomarker signature for MIS-C and may provide new insight into its pathophysiology.
Publisher
Cold Spring Harbor Laboratory
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