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Plasma Protein Biomarkers Distinguish Multisystem Inflammatory Syndrome in Children From Other Pediatric Infectious and Inflammatory Diseases.


ABSTRACT:

Background

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious hyperinflammatory complication following infection with severe acute respiratory syndrome coronavirus 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 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.

Methods

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), Kawasaki disease (n = 23), definite bacterial (n = 28) and viral (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.

Results

Plasma levels of CD163, CXCL9 and PCSK9 were significantly elevated in MIS-C with a combined area under the receiver operating characteristic curve of 85.7% (95% confidence interval: 76.6%-94.8%) for discriminating MIS-C from other childhood diseases. Lower ARG1 and CORIN plasma levels were significantly associated with severe MIS-C cases requiring inotropes, pediatric intensive care unit admission or with shock.

Conclusion

Our findings demonstrate the feasibility of a host protein biomarker signature for MIS-C and may provide new insight into its pathophysiology.

SUBMITTER: Yeoh S 

PROVIDER: S-EPMC11003410 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

Plasma Protein Biomarkers Distinguish Multisystem Inflammatory Syndrome in Children From Other Pediatric Infectious and Inflammatory Diseases.

Yeoh Sophya S   Estrada-Rivadeneyra Diego D   Jackson Heather H   Keren Ilana I   Galassini Rachel R   Cooray Samantha S   Shah Priyen P   Agyeman Philipp P   Basmaci Romain R   Carrol Enitan E   Emonts Marieke M   Fink Colin C   Kuijpers Taco T   Martinon-Torres Federico F   Mommert-Tripon Marine M   Paulus Stephane S   Pokorn Marko M   Rojo Pablo P   Romani Lorenza L   Schlapbach Luregn L   Schweintzger Nina N   Shen Ching-Fen CF   Tsolia Maria M   Usuf Effua E   van der Flier Michiel M   Vermont Clementien C   von Both Ulrich U   Yeung Shunmay S   Zavadska Dace D   Coin Lachlan L   Coin Lachlan L   Cunnington Aubrey A   Herberg Jethro J   Levin Michael M   Kaforou Myrsini M   Hamilton Shea S  

The Pediatric infectious disease journal 20240207 5


<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. 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 or severe bacterial and viral infections, is challenging due to overlapping clinical and lab  ...[more]

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