Cell-free DNA reveals distinct pathology of multisystem inflammatory syndrome in children
Multisystem inflammatory syndrome in children (MIS-C) is a rare but life- threatening hyperinflammatory condition induced by infection with severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) that causes pediatric COVID-19 (pCOVID-19). The relationship of the systemic tissue injury to the...
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Published in | The Journal of clinical investigation Vol. 133; no. 21 |
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Main Authors | , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
American Society for Clinical Investigation
01.11.2023
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Subjects | |
Online Access | Get full text |
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Summary: | Multisystem inflammatory syndrome in children (MIS-C) is a rare but life- threatening hyperinflammatory condition induced by infection with severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) that causes pediatric COVID-19 (pCOVID-19). The relationship of the systemic tissue injury to the pathophysiology of MIS-C is poorly defined. We leveraged the high sensitivity of epigenomics analyses of plasma cell-free DNA (cfDNA) and plasma cytokine measurements to identify the spectrum of tissue injury and glean mechanistic insights. Compared with pediatric healthy controls (pHCs) and patients with pCOVID-19, patients with MIS-C had higher levels of cfDNA primarily derived from innate immune cells, megakaryocyte-erythroid precursor cells, and nonhematopoietic tissues such as hepatocytes, cardiac myocytes, and kidney cells. Nonhematopoietic tissue cfDNA levels demonstrated significant interindividual variability, consistent with the heterogenous clinical presentation of MIS-C. In contrast, adaptive immune cell-derived cfDNA levels were comparable in MIS-C and pCOVID-19 patients. Indeed, the cfDNA of innate immune cells in patients with MIS-C correlated with the levels of innate immune inflammatory cytokines and nonhematopoietic tissue- derived cfDNA, suggesting a primarily innate immunity-mediated response to account for the multisystem pathology. These data provide insight into the pathogenesis of MIS-C and support the value of cfDNA as a sensitive biomarker to map tissue injury in MIS-C and likely other multiorgan inflammatory conditions. |
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ISSN: | 1558-8238 0021-9738 1558-8238 |
DOI: | 10.1172/JCI171729 |