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Pediatr Infect Dis J . Plasma Protein Biomarkers Distinguish Multisystem Inflammatory Syndrome in Children From Other Pediatric Infectious and Infl

tetano

Editor, Senior Moderator
Pediatr Infect Dis J


. 2024 Feb 7.
doi: 10.1097/INF.0000000000004267. Online ahead of print. Plasma Protein Biomarkers Distinguish Multisystem Inflammatory Syndrome in Children From Other Pediatric Infectious and Inflammatory Diseases

Sophya Yeoh[SUP] 1 [/SUP], Diego Estrada-Rivadeneyra[SUP] 1 2 [/SUP], Heather Jackson[SUP] 1 3 [/SUP], Ilana Keren[SUP] 1 [/SUP], Rachel Galassini[SUP] 1 [/SUP], Samantha Cooray[SUP] 1 3 [/SUP], Priyen Shah[SUP] 1 3 [/SUP], Philipp Agyeman[SUP] 4 [/SUP], Romain Basmaci[SUP] 5 6 [/SUP], Enitan Carrol[SUP] 7 [/SUP], Marieke Emonts[SUP] 8 2 9 [/SUP], Colin Fink[SUP] 10 [/SUP], Taco Kuijpers[SUP] 11 12 [/SUP], Federico Martinon-Torres[SUP] 13 14 15 [/SUP], Marine Mommert-Tripon[SUP] 16 [/SUP], Stephane Paulus[SUP] 17 [/SUP], Marko Pokorn[SUP] 18 [/SUP], Pablo Rojo[SUP] 19 [/SUP], Lorenza Romani[SUP] 20 [/SUP], Luregn Schlapbach[SUP] 21 22 [/SUP], Nina Schweintzger[SUP] 23 [/SUP], Ching-Fen Shen[SUP] 24 [/SUP], Maria Tsolia[SUP] 25 [/SUP], Effua Usuf[SUP] 26 [/SUP], Michiel van der Flier[SUP] 27 [/SUP], Clementien Vermont[SUP] 28 [/SUP], Ulrich von Both[SUP] 29 [/SUP], Shunmay Yeung[SUP] 30 [/SUP], Dace Zavadska[SUP] 31 [/SUP], Lachlan Coin[SUP] 32 [/SUP], Aubrey Cunnington[SUP] 1 3 [/SUP], Jethro Herberg[SUP] 1 3 [/SUP], Michael Levin[SUP] 1 3 [/SUP], Myrsini Kaforou[SUP] 1 3 [/SUP], Shea Hamilton[SUP] 1 3 [/SUP]; PERFORM; DIAMONDS and UK KD Genetic Consortia



Affiliations
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.


 
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