Zonulin as a biomarker and potential therapeutic target in multisystem inflammatory syndrome in children
Tiffany Hensley-McBain, Jennifer A. Manuzak
Tiffany Hensley-McBain, Jennifer A. Manuzak
Published June 23, 2021
Citation Information: J Clin Invest. 2021;131(14):e151467. https://doi.org/10.1172/JCI151467.
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Commentary

Zonulin as a biomarker and potential therapeutic target in multisystem inflammatory syndrome in children

Abstract

Multisystem inflammatory syndrome in children (MIS-C) occurs during or recently following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is characterized by persistent fever, inflammation, and severe illness requiring hospitalization. The majority of patients with MIS-C also present with gastrointestinal (GI) symptoms, including abdominal pain, vomiting, and diarrhea. In this issue of the JCI, Yonker, Gilboa, and colleagues identified zonulin as a biomarker of GI permeability in children with MIS-C and present the results of an intriguing proof-of-concept study indicating that zonulin may represent a potential therapeutic target for MIS-C treatment and prevention. Their findings suggest that intestinal mucosal dysfunction and epithelial barrier breakdown may represent a biological mechanism underlying the development of MIS-C in SARS-CoV-2–infected children.

Authors

Tiffany Hensley-McBain, Jennifer A. Manuzak

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Figure 1

Potential model of zonulin-dependent intestinal permeability in MIS-C.

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Potential model of zonulin-dependent intestinal permeability in MIS-C. I...
In healthy children, an intact epithelial barrier separates the lumen of the gut and the commensal microbiome from homeostatic immune cells that reside in the lamina propria. In some children with SARS-CoV-2 infection or exposure, zonulin-dependent intestinal barrier breakdown results in elevated plasma zonulin levels and may allow for SARS-CoV-2 and S1 spike antigen, as well as other gut-residing microbes and microbial particles, to translocate into the circulation. Subsequent activation of inflammatory immune cells may contribute to the development of MIS-C.