MIS-C patients have deeply dysregulated protein profiles, according to new research

Credit: Pixabay/CC0 Public Domain

Levels of proteins in the plasma of patients with multisystem inflammatory syndrome in children (MIS-C) are significantly dysregulated and share features with two other inflammatory syndromes, according to a new study by researchers at Children's Hospital of Philadelphia (CHOP). The findings were recently published in Nature Communications.

MIS-C emerged as the major pediatric complication of SARS-CoV-2 and is characterized by fever, severe inflammation, cardiac dysfunction, and shock. CHOP researchers previously demonstrated that infection with SARS-CoV-2 and MIS-C are associated with thrombotic microangiopathy (TMA), a syndrome that involves clotting in small blood vessels and has been identified as a potential cause for severe manifestations of COVID-19 in adults. However, the mechanism of TMA in the context of MIS-C is unknown, and its association with cytokine dysregulation remains unclear.

To better understand the cytokine dysregulation in MIS-C and its association with TMA, the researchers analyzed the plasma protein landscape of patients with MIS-C, severe COVID-19, mild or asymptomatic COVID-19, and otherwise healthy controls. Analyzing more than 1,400 , the researchers found that protein signatures of patients with MIS-C overlap with those of patients with macrophage activation syndrome (MAS). In fact, a subset of patients with MIS-C satisfied the modified criteria for the diagnosis of MAS.

Moreover, similarly to MAS, IFN-γ (and one of its downstream proteins, CXCL9) were shown to be dysregulated in MIS-C patients. The researchers also found that levels of IFN-γ may also predict the severity of cardiac dysfunction in patients with MIS-C; paradoxically, they observed that patients who had higher IFN-γ levels displayed better cardiac function than those with lower IFN-γ levels.

Finally, the researchers identified the protein PLA2G2A as a candidate biomarker for MIS-C. They found that levels of PLA2G2A are markedly high in almost all patients with MIS-C and differentiate MIS-C patients from other SARS-CoV-2 infected patients, making PLA2G2A a potential biomarker for MIS-C.

"We have made several observations about the underlying pathophysiology of MIS-C, and our future studies will hopefully identify the mechanistic relationships between IFN-γ, PLA2G2A, and other drivers of MIS-C initiation and immunopathology" said Hamid Bassiri, MD, PhD, an attending physician in the Division of Infectious Diseases at Children's Hospital of Philadelphia and co-senior author of the study, along with David T. Teachey, MD, and Edward M. Behrens, MD. "In particular, it will be important to understand the mechanism of PLA2G2A in MIS-C pathophysiology, since PLA2G2A and its associated pathways can be targeted with the common, inexpensive medication indomethacin."

More information: Caroline Diorio et al, Proteomic profiling of MIS-C patients indicates heterogeneity relating to interferon gamma dysregulation and vascular endothelial dysfunction, Nature Communications (2021). DOI: 10.1038/s41467-021-27544-6

Journal information: Nature Communications

Citation: MIS-C patients have deeply dysregulated protein profiles, according to new research (2022, January 24) retrieved 9 December 2023 from https://medicalxpress.com/news/2022-01-mis-c-patients-deeply-dysregulated-protein.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.

Explore further

Elevated biomarker for blood vessel damage found in all children with SARS-CoV-2


Feedback to editors