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- Title
Similarities and differences between the immunopathogenesis of COVID-19-related pediatric multisystem inflammatory syndrome and Kawasaki disease.
- Authors
Esteve-Sole, Ana; Anton, Jordi; Pino-Ramirez, Rosa Maria; Sanchez-Manubens, Judith; Fumadó, Victoria; Fortuny, Claudia; Rios-Barnes, María; Sanchez-de-Toledo, Joan; Girona-Alarcón, Mónica; Mosquera, Juan Manuel; Ricart, Silvia; Launes, Cristian; Fernández de Sevilla, Mariona; Jou, Cristina; Muñoz-Almagro, Carmen; González-Roca, Eva; Vergara, Andrea; Carrillo, Jorge; Juan, Manel; Cuadras, Daniel
- Abstract
Multisystem inflammatory syndrome associated with the SARS-CoV-2 pandemic has recently been described in children (MIS-C), partially overlapping with Kawasaki disease (KD). We hypothesized that (a) MIS-C and prepandemic KD cytokine profiles may be unique and justify the clinical differences observed, and (b) SARS-CoV-2-specific immune complexes (ICs) may explain the immunopathology of MIS-C. Seventy-four children were included: 14 with MIS-C, 9 patients positive for SARS-CoV-2 by PCR without MIS-C (COVID), 14 with prepandemic KD, and 37 healthy controls (HCs). Thirty-four circulating cytokines were quantified in pretreatment serum or plasma samples and the presence of circulating SARS-CoV-2 ICs was evaluated in MIS-C patients. Compared with HCs, the MIS-C and KD groups showed most cytokines to be significantly elevated, with IFN-γ-induced response markers (including IFN-γ, IL-18, and IP-10) and inflammatory monocyte activation markers (including MCP-1, IL-1α, and IL-1RA) being the main triggers of inflammation. In linear discriminant analysis, MIS-C and KD profiles overlapped; however, a subgroup of MIS-C patients (MIS-Cplus) differentiated from the remaining MIS-C patients in IFN-γ, IL-18, GM-CSF, RANTES, IP-10, IL-1α, and SDF-1 and incipient signs of macrophage activation syndrome. Circulating SARS-CoV-2 ICs were not detected in MIS-C patients. Our findings suggest a major role for IFN-γ in the pathogenesis of MIS-C, which may be relevant for therapeutic management.
- Subjects
MUCOCUTANEOUS lymph node syndrome; MACROPHAGE activation syndrome; FISHER discriminant analysis; COVID-19 pandemic; COVID-19; SARS-CoV-2
- Publication
Journal of Clinical Investigation, 2021, Vol 131, Issue 6, p1
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI144554