Post-infectious inflammatory disease in MIS-C features elevated cytotoxicity signatures and autoreactivity that correlates with severity
Anjali Ramaswamy; Nina N. Brodsky; Tomokazu S. Sumida; Michela Comi; Hiromitsu Asashima; Kenneth B. Hoehn; Ningshan Li; Yunqing Liu; Aagam Shah; Neal G. Ravindra; Jason Bishai; Alamzeb Khan; William Lau; Brian Sellers; Neha Bansal; Rachel Sparks; Avraham Unterman; Victoria Habet; Andrew J. Rice; Jason Catanzaro; Harsha Chandnani; Merrick Lopez; Naftali Kaminski; Charles S. Dela Cruz; John S. Tsang; Zuoheng Wang; Xiting Yan; Steven H. Kleinstein; David van Dijk; Richard W. Pierce; David A. Hafler; Carrie L. Lucas.
Preprint
en Inglés
| PREPRINT-MEDRXIV | ID: ppmedrxiv-20241364
Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV2 infection in otherwise healthy children. Here, we define immune abnormalities in MIS-C compared to adult COVID-19 and pediatric/adult healthy controls using single-cell RNA sequencing, antigen receptor repertoire analysis, unbiased serum proteomics, and in vitro assays. Despite no evidence of active infection, we uncover elevated S100A-family alarmins in myeloid cells and marked enrichment of serum proteins that map to myeloid cells and pathways including cytokines, complement/coagulation, and fluid shear stress in MIS-C patients. Moreover, NK and CD8 T cell cytotoxicity genes are elevated, and plasmablasts harboring IgG1 and IgG3 are expanded. Consistently, we detect elevated binding of serum IgG from severe MIS-C patients to activated human cardiac microvascular endothelial cells in culture. Thus, we define immunopathology features of MIS-C with implications for predicting and managing this SARS-CoV2-induced critical illness in children.
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