Innate immune dysregulation in multisystem inflammatory syndrome in children (MIS-C)

Abstract

MIS-C is a systemic inflammation disorder with poorly characterised immunopathological mechanisms. We compared changes in the systemic immune response in children with MIS-C (n = 12, 5–13 years) to healthy controls (n = 14, 5–15 years). Analysis was done in whole blood treated with LPS. Expression of CD11b and Toll-like receptor-4 (TLR4) in neutrophils and monocytes were analysed by flow cytometry. Serum cytokines (IL-1β, IL-2, IL-6, IL-8, IL-10, IL-Ira, TNF-α, TNF-β, IFN-Υ, VEGF, EPO and GM-CSF) and mRNA levels of inflammasome molecules (NLRP3, ASC and IL-1β) were evaluated. Subpopulations of lymphocytes (CD3+, CD19+, CD56+, CD4+, CD8+, TCR Vδ1+, TCR Vδ2+) were assessed at basal levels. Absolute counts of neutrophils and NLR were high in children with MIS-C while absolute counts of lymphocytes were low. Children with MIS-C had increased levels of IL-6, IL-10, TNF-β and VEGF serum cytokines at the basal level, and significantly increased TNF-β post-LPS, compared to controls. IL-1RA and EPO decreased at baseline and post-LPS in MIS-C patients compared to controls. The percentage of CD3+ cells, NK cells and Vδ1 was lower while B cells were higher in children with MIS-C than in controls. Dysregulated immune response in children with MIS-C was evident and may be amenable to immunomodulation.

Programmed Cell Death Protein-1 Regulation in Response to SARS-CoV-2 in Paediatric Multisystem Inflammatory Syndrome Temporally Associated with SARS-CoV-2: A Prospective Cohort Study

“…Children with PIMS-TS had a decreased percentage of CD3+ cells, NK cells and Vδ1 compared to controls [ 21 ]. Rybkina et al found similar results, with a suggestion of a potential role for tissue-derived T cells in the treatment of PIMS-TS.…”

Altered Inflammasome and Immune activation in Paediatric Traumatic Brain Injury

“…The expression of TLR4 and CD11b antigens on the surface of neutrophils and monocytes was evaluated by ow cytometry. Neutrophils were delineated based on SSC-A and CD66b + positivity as previously described [16], and monocytes were de ned based on SSC-A and CD66b negativity and their subsets based on CD14 and CD16 expression: classical (CD14+/CD16-), intermediate (CD14+/CD16+) and nonclassical (CD14dim/CD16+) [17]. A minimum of 10,000 events were collected, and relative expression of TLR4 and CD11b was expressed as mean uorescence intensity (MFI).…”