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Myeloid-derived suppressor cells and T cell populations in children with Multisystem Inflammatory Syndrome

Abstract

Background

Multisystem inflammatory syndrome in children (MIS-C) represents a hyperinflammatory state that can result in multi-organ dysfunction and death. Myeloid-derived suppressor cells (MDSC) are an immunosuppressive cell population that expands under inflammatory conditions and suppresses T cell function. We hypothesized that MDSC would be increased in children with MIS-C and that MDSC expansion would be associated with T cell lymphopenia.

Methods

We conducted a prospective, observational study. Initial blood samples were collected within 48 h of admission. Age-matched healthy controls underwent sampling once. MDSC and T cell populations were identified by flow cytometric methods.

Results

We enrolled 22 children with MIS-C (12 ICU, 10 ward) and 21 healthy controls (HC). Children with MIS-C demonstrated significantly higher MDSC compared to HC, and MDSC expansion persisted for >3 weeks in the ICU group. Children with MIS-C admitted to the ICU demonstrated significantly lower absolute numbers of T cells and natural killer cells. There were no significant associations between MDSC and cardiac dysfunction, duration of hospitalization, or vasoactive inotrope score.

Conclusions

Our study suggests that children critically ill with MIS-C have expansion of MDSC and associated decreased T cell and NK cell populations. Our results did not demonstrate associations between MDSC and clinical outcomes.

Impact

  • Multisystem inflammatory syndrome in children (MIS-C) is a dysregulated immune response occurring several weeks after SARS-CoV-2 infection that can result in multi-organ dysfunction and death.

  • Children severely ill with MIS-C demonstrated increased myeloid-derived suppressor cells and decreased absolute numbers of CD4+ and CD8 + T cells and NK cells compared to healthy controls.

  • There was no significant association between MDSC numbers and clinical outcomes; including cardiac dysfunction, length of stay, or requirement of vasoactive support, in children with MIS-C.

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Fig. 1: Critically ill children with MIS-C exhibit increased Total MDSC.
Fig. 2: Increased %MDSC of PBMC persists in children critically ill with MIS-C.
Fig. 3: Associations in CD4 + T cell populations in children with MIS-C.
Fig. 4: Associations in CD8 + T cell populations in children with MIS-C.
Fig. 5: Associations between T regulatory cells and NK cells in children with MIS-C.
Fig. 6: Receiver operating characteristic curve demonstrating an optimal cutoff value of 8.3% Total MDSC of PBMC to discriminate between children with and without organ dysfunction.

Data availability

The datasets generated during and/or analyzed during the current study are available form the corresponding author on reasonable request.

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Acknowledgements

We would like to thank the patients and their families for their participation in this study. We also want to express our gratitude for Nationwide Children’s Hospital Clinical Research Services and nursing staff for their efforts in patient recruitment and sample collection.

Funding

This project was made possible by funding from the Thrasher Research Fund.

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Authors and Affiliations

Authors

Contributions

K.B., A.M., and O.R. contributed substantially to conception and design. A.W., A.A., S.M., F.Y., L.S., and A.W. contributed to acquisition of data. K.B. and R.A. contributed to analysis and interpretation of data. K.B. drafted the article. All authors gave final approval of the published version.

Corresponding author

Correspondence to Katherine E. Bline.

Ethics declarations

Competing interests

A.M. has received fees for participation in Advisory Boards from Janssen, Merck, Pfizer, AstraZeneca and Sanofi-Pasteur, grants from NIH, Merck, and Janssen to institutions. O.R. has received research grants to institution from Janssen, Merck, NIH, and the Bill & Melinda Gates Foundation; and fees for participation in Advisory Boards from Sanofi-Pasteur, Merck, and Pfizer and for lectures from Pfizer, Sanofi-Pasteur, Merck, and AstraZeneca.

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Patients were enrolled under an IRB approved protocol and informed consent was signed by legal guardians before participation; assent was obtained when appropriate.

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Bline, K.E., Wilt, A.L., Alexander, R.N. et al. Myeloid-derived suppressor cells and T cell populations in children with Multisystem Inflammatory Syndrome. Pediatr Res (2023). https://doi.org/10.1038/s41390-023-02919-1

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