Emergency Myelopoiesis Distinguishes Multisystem Inflammatory Syndrome in Children From Pediatric Severe Coronavirus Disease 2019

Katerina Roznik, Temesgen E. Andargie, T. Scott Johnston, Oren Gordon, Yi Wang, Nadine Peart Akindele, Deborah Persaud, Annukka A.R. Antar, Yukari C. Manabe, Weiqiang Zhou, Hongkai Ji, Sean Agbor-Enoh, Andrew H. Karaba, Elizabeth A. Thompson, Andrea L. Cox

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition caused by recent infection with severe acute respiratory syndrome coronavirus 2, but the underlying immunological mechanisms driving this distinct syndrome are unknown. Methods. We utilized high-dimensional flow cytometry, cell-free (cf) DNA, and cytokine and chemokine profiling to identify mechanisms of critical illness distinguishing MIS-C from severe acute coronavirus disease 2019 (SAC). Results. Compared to SAC, MIS-C patients demonstrated profound innate immune cell death and features of emergency myelopoiesis (EM), an understudied phenomenon observed in severe inflammation. EM signatures were characterized by fewer mature myeloid cells in the periphery and decreased expression of HLA-DR and CD86 on antigen-presenting cells. Interleukin 27 (IL-27), a cytokine known to drive hematopoietic stem cells toward EM, was increased in MIS-C, and correlated with immature cell signatures in MIS-C. Upon recovery, EM signatures decreased and IL-27 plasma levels returned to normal levels. Despite profound lymphopenia, we report a lack of cfDNA released by adaptive immune cells and increased CCR7 expression on T cells indicative of egress out of peripheral blood. Conclusions. Immune cell signatures of EM combined with elevated innate immune cell-derived cfDNA levels distinguish MIS-C from SAC in children and provide mechanistic insight into dysregulated immunity contributing toward MIS-C, offering potential diagnostic and therapeutic targets.

Original languageEnglish (US)
Pages (from-to)e305-e317
JournalJournal of Infectious Diseases
Volume230
Issue number2
DOIs
StatePublished - Aug 15 2024

Keywords

  • IL-27
  • MIS-C
  • cell-free DNA
  • emergency myelopoiesis
  • pediatric COVID-19

ASJC Scopus subject areas

  • General Medicine

Fingerprint

Dive into the research topics of 'Emergency Myelopoiesis Distinguishes Multisystem Inflammatory Syndrome in Children From Pediatric Severe Coronavirus Disease 2019'. Together they form a unique fingerprint.

Cite this