Cytotoxic lymphocytes are dysregulated in multisystem inflammatory syndrome in children.
Noam D BeckmannPhillip H ComellaEsther ChengLauren LepowAviva G BeckmannKonstantinos MouskasNicole W SimonsGabriel E HoffmanNancy J FrancoeurDiane Marie Del ValleGurpawan KangEmily MoyaLillian WilkinsJessica Le BerichelChristie ChangRobert MarvinSharlene CalorossiAlona LanskyLaura WalkerNancy YiAlex YuMatthew HarnettMelody EatonSandra HatemHajra JamalAlara AkyatanAlexandra TabachnikovaLora E LiharskaLiam CotterBrian FennesseyAkhil VaidGuillermo BarturenScott R TylerHardik ShahYinh-Chih WangShwetha Hara SridharJuan SotoSwaroop BoseKent MadridEthan EllisElyze MerzierKonstantinos VlachosNataly FishmanManying TinMelissa SmithHui XieManishkumar PatelKimberly ArguetaJocelyn HarrisNeha KarekarCraig BatchelorJose LacunzaMahlet YishakKevin TuballesLeisha ScottArvind KumarSuraj JaladankiRyan ThompsonEvan ClarkBojan LosicJun ZhuWenhui WangAndrew KasarskisBenjamin S GlicksbergGirish NadkarniDusan BogunovicCordelia ElaihoSandeep GangadharanGeorge Ofori-AmanfoKasey Alesso-CarraKenan OnelKaren M WilsonCarmen ArgmannMarta E Alarcón-RiquelmeThomas U MarronAdeeb RahmanSeunghee Kim-SchulzeSacha GnjaticBruce D GelbMiriam MeradRobert SebraEric E SchadtAlexander W CharneyPublished in: medRxiv : the preprint server for health sciences (2020)
Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and multiple organ involvement in individuals under 21 years following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To identify genes, pathways and cell types driving MIS-C, we sequenced the blood transcriptomes of MIS-C cases, pediatric cases of coronavirus disease 2019, and healthy controls. We define a MIS-C transcriptional signature partially shared with the transcriptional response to SARS-CoV-2 infection and with the signature of Kawasaki disease, a clinically similar condition. By projecting the MIS-C signature onto a co-expression network, we identified disease gene modules and found genes downregulated in MIS-C clustered in a module enriched for the transcriptional signatures of exhausted CD8 + T-cells and CD56 dim CD57 + NK cells. Bayesian network analyses revealed nine key regulators of this module, including TBX21 , a central coordinator of exhausted CD8 + T-cell differentiation. Together, these findings suggest dysregulated cytotoxic lymphocyte response to SARS-Cov-2 infection in MIS-C.