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Immune Profiles in Multisystem Inflammatory Syndrome in Children with Cardiovascular Abnormalities
Nathella Pavan Kumar1, Aishwarya Venkataraman1, Arul Nancy2
1ICMR-National Institute for Research in Tuberculosis, Chennai 600031, India.
Insights
Multisystem inflammatory syndrome in children (MIS-C) with cardiac involvement shows distinct immune profiles compared to non-cardiac MIS-C. These inflammatory markers normalize after treatment, aiding in understanding MIS-C immunopathogenesis.
Area of Science:
- Pediatric immunology
- Infectious disease pathology
- Cytokine and chemokine research
Background:
- Multisystem inflammatory syndrome in children (MIS-C) is a serious complication following SARS-CoV-2 infection.
- Cardiac involvement is frequent in MIS-C, but immunological distinctions between cardiac and non-cardiac forms are unclear.
- Understanding these immunological differences is crucial for managing MIS-C.
Purpose of the Study:
- To differentiate the immunological profiles of MIS-C with cardiac involvement versus MIS-C without cardiac involvement.
- To identify specific cytokines and chemokines associated with cardiac manifestations in MIS-C.
- To contribute to the understanding of MIS-C immunopathogenesis, particularly in low- and middle-income countries.
Main Methods:
- Analyzed levels of various cytokines (Type 1, 2, 17, pro-inflammatory) and chemokines (CC, CXC) in MIS-C patients.
- Utilized the Magpix multiplex cytokine assay system for measurements.
- Compared immune markers in children with MIS-C cardiac (n=88) and MIS-C non-cardiac (n=64) conditions.
Main Results:
- Children with cardiac MIS-C exhibited significantly higher levels of numerous cytokines (e.g., IFN-γ, IL-6, TNFα) and chemokines (e.g., CCL2, CXCL10).
- Clustering analysis confirmed that cytokine and chemokine patterns effectively distinguished between cardiac and non-cardiac MIS-C.
- Immune responses in MIS-C patients significantly decreased and normalized approximately 9 months post-treatment.
Conclusions:
- This study provides novel insights into the systemic inflammation differentiating cardiac from non-cardiac MIS-C.
- It is among the first studies from a low- and middle-income country to characterize these immunological differences.
- The findings advance the knowledge of MIS-C immunopathogenesis and highlight the potential for immune marker normalization post-treatment.
Background:
Multisystem inflammatory syndrome in children (MIS-C), a sequela of severe acute respiratory syndrome coronavirus-2 infection (SARS-CoV2), has been progressively reported worldwide, with cardiac involvement being a frequent presentation. Although the clinical and immunological characteristics of MIS-C with and without cardiac involvement have been described, the immunological differences between cardiac and non-cardiac MIS-C are not well understood.
Methods:
The levels of type 1, type 2, type 17, other proinflammatory cytokines and CC chemokines and CXC chemokines were measured using the Magpix multiplex cytokine assay system in MIS-C children with MIS-C cardiac (MIS-C (C) (n = 88)) and MIS-C non-cardiac (MIS-C (NC) (n = 64)) abnormalities.
Results:
MIS-C children with cardiac manifestations presented with significantly increased levels of cytokines such as IFN-γ, IL-2, TNFα, IL-5, IL-1α, IL-1β, IL-6, IL-10 and IL-12p70 and chemokines such as CCL2, CCL3, CCL11 and CXCL10 in comparison to MIS-C children without cardiac manifestations. Clustering analysis revealed that cytokines and chemokines could clearly distinguish MIS-C children with and without cardiac manifestations. In addition, these responses significantly diminished and normalized 9 months after treatment.
Conclusions:
This is one of the first studies characterizing and differentiating systemic inflammation in MIS-C with and without cardiac involvement from a low- and middle-income country (LMIC). Our study contributes to the existing body of evidence and advances our knowledge of the immunopathogenesis of MIS-C in children.
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