Similarities and differences between the immunopathogenesis of COVID-19–related pediatric multisystem inflammatory syndrome and Kawasaki disease
Ana Esteve-Sole, … , Iolanda Jordan, Laia Alsina
Ana Esteve-Sole, … , Iolanda Jordan, Laia Alsina
Published January 26, 2021
Citation Information: J Clin Invest. 2021;131(6):e144554. https://doi.org/10.1172/JCI144554.
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Research Article Immunology

Similarities and differences between the immunopathogenesis of COVID-19–related pediatric multisystem inflammatory syndrome and Kawasaki disease

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.

Authors

Ana Esteve-Sole, Jordi Anton, Rosa Maria Pino-Ramirez, Judith Sanchez-Manubens, Victoria Fumadó, Claudia Fortuny, María Rios-Barnes, Joan Sanchez-de-Toledo, Mónica Girona-Alarcón, Juan Manuel Mosquera, Silvia Ricart, Cristian Launes, Mariona Fernández de Sevilla, Cristina Jou, Carmen Muñoz-Almagro, Eva González-Roca, Andrea Vergara, Jorge Carrillo, Manel Juan, Daniel Cuadras, Antoni Noguera-Julian, Iolanda Jordan, Laia Alsina

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Figure 3

Leave-one-out cross-validation of linear discriminant analysis model.

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Leave-one-out cross-validation of linear discriminant analysis model. Ro...
Rows represent the preclassified groups and columns the predicted categories after leave-one-out cross-validation. KD, pre–SARS-CoV-2 pandemic Kawasaki disease (n = 14); MIS-C, multisystem inflammatory syndrome in children (n = 13); COVID, pediatric patients with mild COVID-19 disease without MIS-C (n = 9); HC, healthy controls (n = 31 [53 samples]).