Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and pathology of multiple organs in individuals under 21 years of age in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although an autoimmune pathogenesis has been proposed, the genes, pathways and cell types causal to this new disease remain unknown. Here we perform RNA sequencing of blood from patients with MIS-C and controls to find disease-associated genes clustered in a co-expression module annotated to CD56 dim CD57 + natural killer (NK) cells and exhausted CD8 + T cells. A similar transcriptome signature is replicated in an independent cohort of Kawasaki disease (KD), the related condition after which MIS-C was initially named. Probing a probabilistic causal network previously constructed from over 1,000 blood transcriptomes both validates the structure of this module and reveals nine key regulators, including TBX21, a central coordinator of exhausted CD8 + T cell differentiation. Together, this unbiased, transcriptome-wide survey implicates downregulation of NK cells and cytotoxic T cell exhaustion in the pathogenesis of MIS-C. Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.
【저자키워드】 Inflammation, Prognostic markers, Antimicrobial responses, Systems analysis, 【초록키워드】 Transcriptome, SARS-CoV-2, pathology, coronavirus, Pathogenesis, T cells, children, Infection, NK cell, NK cells, severe acute respiratory syndrome Coronavirus, CD8, MIS-C, Peripheral blood, Cohort, T cell, Kawasaki disease, Fever, RNA sequencing, Patient, Control, pathway, Manifestations, age, respiratory, disease, patients, CD8+ T cell, Blood, Inflammatory, Pathways, COVID-19 patient, manifestation, Cytotoxic T cell, cell types, cell type, transcriptomes, natural killer, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, Author, individual, syndrome, multiple organs, downregulation, CD57, cell activation, CD56, TBX21, autoimmune pathogenesis, probe, Genes, co-expression, Cell, independent, blood transcriptome, nine, replicated, reveal, disease-associated, coordinator, multiple organ, Probing, transcriptome-wide, 【제목키워드】 Gene Expression, children, Inflammatory, syndrome,