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Inflammatory and Autoimmune Aspects of Multisystem Inflammatory Syndrome in Children (MIS-C): A Prospective Cohort
David A Lawrence1,2, Aishwarya Jadhav1, Tapan K Mondal1
1Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA.
Insights
Multisystem Inflammatory Syndrome in Children (MIS-C) involves elevated type-2 cytokines and autoantibodies. These immune responses may explain why some children develop severe MIS-C after COVID-19 infection.
Area of Science:
- Immunology
- Pediatrics
- Infectious Diseases
Background:
- Multisystem Inflammatory Syndrome in Children (MIS-C) is a serious COVID-19 complication.
- The underlying immune mechanisms driving MIS-C severity remain unclear.
Purpose of the Study:
- To compare immune biomarkers between children with MIS-C and those with moderate-severe COVID-19.
- To identify immune molecules contributing to MIS-C development.
Main Methods:
- Analysis of clinical samples from hospitalized children with COVID-19 or MIS-C.
- Enumeration of blood leukocytes and measurement of serum cytokines, chemokines, antibodies, and autoantibodies.
Main Results:
- MIS-C patients showed higher neutrophil/lymphocyte and eosinophil/lymphocyte ratios.
- Elevated IgM and IgA to SARS-CoV-2 RBD, and higher levels of type-2 cytokines (IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-33) were observed in MIS-C.
- Increased IgG autoantibodies to brain antigens, pentraxin, and anti-caspr2 were found in MIS-C patients.
Conclusions:
- Type-2 inflammation and autoantibody production may play a role in MIS-C pathogenesis.
- Autoimmune responses could contribute to the severe manifestations of MIS-C in some children.
- Further research is needed to elucidate triggers of autoimmunity and type-2 inflammation in MIS-C.
Abstract:
Multisystem Inflammatory Syndrome in Children (MIS-C) is a potentially life-threatening complication of COVID-19. The pathophysiological mechanisms leading to severe disease are poorly understood. This study leveraged clinical samples from a well-characterized cohort of children hospitalized with COVID-19 or MIS-C to compare immune-mediated biomarkers. Our objective was to identify selected immune molecules that could explain, in part, why certain SARS-CoV-2-infected children developed MIS-C. We hypothesized that type-2 helper T cell-mediated inflammation can elicit autoantibodies, which may account for some of the differences observed between the moderate-severe COVID-19 (COVID+) and MIS-C cohort. We enumerated blood leukocytes and measured levels of selected serum cytokines, chemokines, antibodies to COVID-19 antigens, and autoantibodies in children presenting to an academic medical center in Connecticut, United States. The neutrophil/lymphocyte and eosinophil/lymphocyte ratios were significantly higher in those in the MIS-C versus COVID+ cohort. IgM and IgA, but not IgG antibodies to SARS-CoV-2 receptor binding domain were significantly higher in the MIS-C cohort than the COVID+ cohort. The serum levels of certain type-2 cytokines (interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10, IL-13, and IL-33) were significantly higher in children with MIS-C compared to the COVID+ and SARS-CoV-2-negative cohorts. IgG autoantibodies to brain antigens and pentraxin were higher in children with MIS-C compared to SARS-CoV-19-negative controls, and children with MIS-C had higher levels of IgG anti-contactin-associated protein-like 2 (caspr2) compared to the COVID+ and SARS-CoV-19-negative controls. We speculate that autoimmune responses in certain COVID-19 patients may induce pathophysiological changes that lead to MIS-C. The triggers of autoimmunity and factors accounting for type-2 inflammation require further investigation.
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