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Sex-specific differences in systemic immune responses in MIS-C children
Anuradha Rajamanickam1, Nathella Pavan Kumar2, Aishwarya Venkataraman2
1National Institutes of Health-National Institute for Research in Tuberculosis - International Center for Excellence in Research, Chennai, India. anuradha@icerindia.org.
Insights
Male children with Multisystem Inflammatory Syndrome (MIS-C) exhibit a more robust immune response compared to females. This heightened inflammatory profile in boys may explain sex-based differences in MIS-C disease development and outcomes.
Area of Science:
- Pediatric Immunology
- Infectious Diseases
- COVID-19 Research
Background:
- Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe complication of SARS-CoV-2 infection.
- Sex disparities are noted in COVID-19 outcomes, but MIS-C immune responses by sex are understudied.
Purpose of the Study:
- To investigate sex-specific differences in immune parameters among children diagnosed with MIS-C.
- To identify immune markers associated with sex in the context of MIS-C.
Main Methods:
- An observational, cross-sectional study design was employed.
- Key immune parameters including cytokines, chemokines, acute phase proteins, growth factors, microbial translocation markers, complement components, and matrix metalloproteinases were analyzed in relation to patient sex.
Main Results:
- Male children with MIS-C showed significantly higher levels of pro-inflammatory cytokines (e.g., IFNγ, IL-6, TNFα), chemokines (e.g., CXCL8, CCL2), acute phase proteins (e.g., CRP), and microbial translocation markers compared to females.
- Elevated levels of growth factors, complement components, and matrix metalloproteinases were also observed in males.
Conclusions:
- A heightened immune response, characterized by elevated inflammatory markers, is a distinct feature in male children with MIS-C.
- These sex-specific immune profiles may contribute to differential disease pathogenesis and clinical outcomes in MIS-C.
Abstract:
Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare manifestation of Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) infection that can result in increased morbidity and mortality. Mounting evidence describes sex disparities in the clinical outcomes of coronavirus disease 2019 (COVID-19). However, there is a lack of information on sex-specific differences in immune responses in MIS-C. This study is an observational and cross-sectional study and we wanted to examine immune parameters such as cytokines, chemokines, acute phase proteins (APPs), growth factors, microbial translocation markers (MTMs), complement components and matrix metalloproteinases (MMPs) in MIS-C children, based on sex. Male children were associated with heightened levels of pro-inflammatory cytokines-IFNγ, IL-2, TNFα, IL-1α, IL-1β, IL-6, IL-12, G-CSF and GM-CSF, chemokines-CCL2, CCL11, CXCL1, CXCL8 and CXCL10, acute phase proteins-α-2M, CRP, growth factors VEGF and TGFα, microbial translocation markers- iFABP, LBP, EndoCAb, complement components-C1q, MBL and C3 and matrix metalloproteinases MMP-8 and MMP-9 compared to female children with MIS-C. These results indicate that the heightened immune response in males is a characteristic feature of MIS-C. These findings might explain the differential disease pathogenesis in males compared to females with MIS-C and facilitate a deeper understanding of this disease.
