Immunology of Multisystem Inflammatory Syndrome after COVID-19 in Children: A Review of the Current Evidence
Abstract
:1. Introduction
2. Incidence of MIS-C
3. Innate Immune Responses in MIS-C
4. Humoral Immune Responses in MIS-C
5. Cellular Immune Response in MIS-C
6. SARS-CoV-2 Spike Protein as a Superantigen in MIS-C
7. MIS-C and COVID-19 Vaccination
8. Genetic Factors Associated with MIS-C
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Immune System Aspects | Immunological Factors in MIS-C | References |
---|---|---|
Innate immunity | Lymphopenia, neutrophilia, elevated inflammatory markers, thrombocytopenia and low eosinophil counts | [22,23,24] |
Increased expression of CD11b, CD66b, LAIR-1, and PD-L1 in neutrophils | [25] | |
CCRL2, ELMO2, GPR84, IRF7, IFIT3, and MX1 genes upregulation | [26] | |
Reduced antigen-presenting cells | [27] | |
Increased neutrophil extracellular traps | [28,29] | |
Increased signaling pathways (NF-kB, VEGF, IFN, IL-1, IL-6, and IL-17) | [30] | |
NK cells: increased expression of CCL4, NCR1 | [27,31] | |
Evelated cytokines (TNF, TRAIL, IL-7, IL-2, IL-13, IFN-g, IFN-a2, IL-17A, Granzyme B, IL-8, IL-10) | [15,16,27,30,32,33,34,35] | |
Elevated chemokines (CCL2, CCL3, CCL4, CXCL1, CXCL5, CXCL6, CXCL9, CXCL10, CXCL11, CX3CL1, CX10, CCL20) | [15,16,27,30,32,33,34,35] | |
Increased expression of IFN-stimulated genes in dendritic cells and monocytes: JAK2, STAT1, STAT2, IFITM1, IFITM2, IFI35, IFIT1, IFIT3, MX1, IRF1 | [30] | |
Increased phospholipase A2 (PLA2G2A) | [31] | |
Increased soluble C5b-9 | [36] | |
Humoral Immunity | Higher SARS-CoV-2 and IgA antibody levels, lower IgM compared to non-MIS-C patients | [37,38,39] |
Higher SARS-CoV-2 anti-S IgG compared to anti-N IgG levels in MIS-C | [33,39,40] | |
Comparable SARS-CoV-2 anti-S IgG, anti-S IgM and anti-N IgG levels to non-MIS-C patients | [39] | |
Increased autoantibodies against Type I IFNs, IL-1Ra | [41,42,43] | |
Cellular immunity | Increased CD4+ and CD8+ T cells | [44,45,46] |
Increased B-cell plasmablasts | [45] | |
Increased CD8+ T cells cytotoxicity | [47] | |
Increased CX3CR1+CD8+ T cells | [45] | |
Increased CD8+ T cell-mediated IFN-gamma | [48] | |
Superantigen | High affinity of SARS-CoV-2 Spike protein to TCR | [49] |
Εnhancement of TRBV11-2 in T cells | [47,50,51,52] |
Immunological Factors | MIS-C | Kawasaki Disease | References |
---|---|---|---|
Absolute neutrophil counts | ↓ | ↑ | [24] |
Absolute lymphocyte counts | ↓ | ↑ | [24] |
Absolute platelet counts | ↓ | ↑ | [24] |
Absolute eosinophil counts | ↓ | ↑ | [24] |
IFN-gamma CXCL9 values | ↑ | ↓ | [53] |
IL-1 and IL-8 | ↑ | ↑ | [24] |
TNF-a, IFN-gamma and IL-10 | ↑ | ↑ | [24,54] |
IL-17 | ↑ | ↑ | [53] |
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Filippatos, F.; Tatsi, E.-B.; Michos, A. Immunology of Multisystem Inflammatory Syndrome after COVID-19 in Children: A Review of the Current Evidence. Int. J. Mol. Sci. 2023, 24, 5711. https://doi.org/10.3390/ijms24065711
Filippatos F, Tatsi E-B, Michos A. Immunology of Multisystem Inflammatory Syndrome after COVID-19 in Children: A Review of the Current Evidence. International Journal of Molecular Sciences. 2023; 24(6):5711. https://doi.org/10.3390/ijms24065711
Chicago/Turabian StyleFilippatos, Filippos, Elizabeth-Barbara Tatsi, and Athanasios Michos. 2023. "Immunology of Multisystem Inflammatory Syndrome after COVID-19 in Children: A Review of the Current Evidence" International Journal of Molecular Sciences 24, no. 6: 5711. https://doi.org/10.3390/ijms24065711
APA StyleFilippatos, F., Tatsi, E. -B., & Michos, A. (2023). Immunology of Multisystem Inflammatory Syndrome after COVID-19 in Children: A Review of the Current Evidence. International Journal of Molecular Sciences, 24(6), 5711. https://doi.org/10.3390/ijms24065711