Background: Multisystem inflammatory syndrome (MIS-C) is an acute, febrile, SARS-CoV-2 associated syndrome, often with cardio-hemodynamic dysfunction. Insight into mechanism of disease is still incomplete. Objective: Our objective was to analyze immunologic features of MIS-C patients compared to febrile controls (FC). Methods: MIS-C patients were defined by narrow criteria, including having evidence of cardio-hemodynamic involvement and no macrophage activation syndrome (MAS). Samples were collected from eight completely treatment-naive patients with MIS-C (SARS-CoV-2 serology positive), three patients with unclassified “MIS-C-like” disease (serology negative), 14 FC, and 5 MIS-C recovery (RCV). Three healthy controls (HC) were used for normal range comparisons. Using spectral flow cytometry, we assessed 36 parameters in antigen presenting cells (APC) and 29 in T cells. We used biaxial analysis and Uniform Manifold Approximation and Projection (UMAP). Results: Significant elevations in cytokines including CXCL9, M-CSF and IL27 were found in MIS-C compared to FC. Classic monocytes and dendritic cell (DC) type 2 were downregulated (decreased CD86, HLA-DR) vs HC, however DC1 (CD11c+CD141+CLEC9A+) were highly activated in MIS-C patients vs FC, expressing higher levels of CD86, CD275, and atypical conventional dendritic cell (cDC) markers such as CD64, CD115, and CX3CR1. CD169 and CD38 were upregulated on multiple monocyte subtypes. CD56dim/CD57-/KLRGhi/CD161+/CD38- NK cells were a unique subset in MIS-C vs FC without MAS. Conclusion: Orchestrated by complex cytokine signaling, DC1 activation and NK dysregulation are key features in the pathophysiology of MIS-C. NK cell findings may suggest a relationship with MAS, while DC1 upregulation implies a role for antigen cross presentation.

Fuente: Journal of Allergy and Clinical Immunology
Available online 22 October 2021