Persistent immune dysregulation consistent with chronic low-grade inflammation in paediatric burn survivors

Objectives To characterise long-term immune dysregulation and persistent inflammatory signalling in paediatric burn survivors with hypertrophic scarring. Methods Peripheral blood mononuclear cells and plasma were analysed from 20 paediatric participants: 10 burn survivors with hypertrophic scarring (median 4.1 years post-injury) and 10 age- and sex-matched healthy controls. Multiparameter flow cytometry, multiplex cytokine analysis, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to assess immune cell phenotypes, inflammatory mediators, and inflammatory gene expression. Results Overall proportions of major immune cell subsets were comparable between groups. However, burn survivors with hypertrophic scarring demonstrated increased CD4⁺TNFα⁺ cells, Th17 cells, CCR6⁺ natural killer T-like cells, IL-23⁺ natural killer cells, and IL-23-expressing macrophage populations (all P<0.05). Regulatory T cells (Tregs) and CCR4⁺CCR6⁺ double-positive Tregs were also increased (P<0.05). Plasma concentrations of IL-1β, tumour necrosis factor-α, IL-12p70, IL-17A, and IL-23 were significantly elevated in the scar group (all P<0.05). Gene expression analysis identified persistent upregulation of nuclear factor kappa B1 (NFκB1; 2.21-fold) and IL-17 (3.38-fold). Conclusion Paediatric burn survivors with hypertrophic scarring demonstrate persistent systemic immune dysregulation several years after injury. However, the cross-sectional design and absence of a normotrophic burn control group limit conclusions regarding whether these immune alterations are specific to pathological scarring or reflect broader long-term post-burn immune dysregulation.