{"doi":"10.1172/jci171729","title":"Cell-free DNA reveals distinct pathology of multisystem inflammatory syndrome in children","abstract":"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.","journal":"Journal of Clinical Investigation","year":2023,"id":344907,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":922642,"name":"Katerina Roznik","orcid":"0000-0002-5403-8747","position":1,"is_corresponding":false},{"id":1001264,"name":"Neelam Redekar","orcid":"0000-0002-4819-9034","position":2,"is_corresponding":false},{"id":376615,"name":"Tom Hill","orcid":"0000-0002-4661-6391","position":3,"is_corresponding":false},{"id":351832,"name":"Weiqiang Zhou","orcid":"0000-0001-9396-9571","position":4,"is_corresponding":false},{"id":1084262,"name":"Zainab Apalara","orcid":null,"position":5,"is_corresponding":false},{"id":627891,"name":"Hyesik Kong","orcid":"0000-0001-7540-2045","position":6,"is_corresponding":false},{"id":506158,"name":"Oren Gordon","orcid":"0000-0002-3159-8426","position":7,"is_corresponding":false},{"id":885198,"name":"Rohan Meda","orcid":null,"position":8,"is_corresponding":false},{"id":1083840,"name":"Woojin Park","orcid":"0000-0001-9982-0057","position":9,"is_corresponding":false},{"id":858772,"name":"Trevor S. 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