Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem...

Area of Science:

• Immunology
• Pediatric Infectious Diseases
• Molecular Biology

Background:

• Multisystem inflammatory syndrome in children (MIS-C) is a severe post-infectious complication of SARS-CoV-2.
• MIS-C onset is unpredictable, occurring weeks after infection, even in asymptomatic cases.

Purpose of the Study:

• To identify molecular and cellular signatures associated with MIS-C.
• To correlate these signatures with disease severity.
• To explore potential diagnostic and prognostic biomarkers for MIS-C.

Main Methods:

• Single-cell RNA sequencing
• Flow cytometry
• Antigen receptor repertoire analysis
• Serum proteomics

Main Results:

• MIS-C patients exhibited elevated S100A alarmins and impaired antigen presentation, suggesting myeloid dysfunction.
• Increased cytotoxicity gene expression in NK and CD8+ T cells and expanded IgG-expressing plasmablasts were observed.
• Severe MIS-C cases showed skewed T-cell receptor repertoires and endothelium-reactive IgG, indicating autoimmunity.

Conclusions:

• Defined signatures including alarmins, cytotoxicity, T-cell receptor repertoires, and plasmablasts show potential for early MIS-C diagnosis and severity prediction.
• These findings highlight key immune dysregulations in MIS-C.
• Further research can translate these signatures into clinical tools for managing MIS-C.