Epidemiological studies conducted within Australia have demonstrated that survivors of burn injuries, regardless of severity, are at a long-term risk of cardiovascular disease, infections, and other morbidities. However, the mechanisms underlying this pattern of diseases are poorly understood. We hypothesised that burn injury results in an enduring change to the immunoinflammatory and thrombotic systems.
We investigated changes to circulating cytokines in 38 paediatric burn survivors at least 3 years post-injury vs age/sex-matched healthy controls. TNF (1.2-1.6 -fold). Burn patients demonstrated diminished IgG titres and rates of protection to the diphtheria, tetanus, and pertussis vaccine. A bespoke mass cytometry panel of 40 antibodies was used to characterise PBMCs from 22 of these patients and barcoded, matched controls. Comparisons by unsupervised FlowSOM showed concordance of major PBMC subsets between burn and control, but identified disparity in clusters corresponding to naïve and memory T-cell subsets, and subpopulations of B-cells. Furthermore, memory T-regulatory cells, Th17 cells, central memory CD8+ T cells, and central memory CD4+ T cells were all generally elevated (0.05 < p < 0.1) in the burn cohort.
In a mouse model of non-severe burn injury (NSBI, 8% full-thickness) we demonstrate increased responsiveness of platelets as expression of CD62P upon stimulation of the platelet collagen receptor (1.2-fold change from sham) at 28 days post-injury. Preliminary data from 21 adult human patients vs uninjured controls supports this finding, with increased platelet activation following collagen receptor stimulation (as shown by PAC1 binding, 2.1-fold, p < 0.05)) and increased circulating monocyte-platelet aggregates (1.6-fold, p<0.05). There was a non-significant trend toward increased responsiveness to collagen-related peptide at 6 weeks.
We provide evidence for an enduring change to the immune profile of paediatric burn survivors, and elevated platelet responsiveness in both mice and humans, following NSBI.