Unravelling the mechanisms behind burn-associated immune dysfunction


Lucy Barrett1,2,3, Blair Johnson1,3,
1Burn Injury Research Unit, University of Western Australia, Perth, WA, Australia
2Paediatric Burn Care, Telethon Kids Institute, Perth, WA, Australia
3Fiona Wood Foundation, Perth, WA, Australia

Abstract

Burn patients have a reduced life expectancy and are at increased risk of infections, cancer, and other diseases long after discharge from hospital for the burn injury itself. Of particular concern, these risks are also associated with non-severe burn injuries so understanding the mechanisms behind this is a priority. We have built a strong evidence base using pre-clinical burn models, patient studies and epidemiology to show that the immune system is compromised for many years after a burn. We believe this is the cause of susceptibility to chronic disease seen in children after a burn. However, we still do not fully understand the underlying mechanisms that lead to immune dysfunction after burn trauma, meaning children cannot be treated to reduce these known long-term health impacts.

In paediatric patients, analysis of blood samples taken >3 years post-injury shows burn patients have reduced or absent responses to vaccine antigens (Diptheria, Tetanus, Pertussis) despite receiving their DTaP vaccine >1 year after injury. Additionally, preliminary analysis of circulating immune cell profiles in blood samples taken on admission to hospital for the burn have identified changes in immune cell subsets that correlate with short-term outcomes during burn healing, and may be used to predict poor long-term immunity outcomes. By expanding this study, performing in-depth analysis of circulating immune cells and metabolic profiles before and after vaccination, and utilising functional assays to interrogate immune cell capability and plasticity, we hope to develop a strategy to identify at-risk patients in the future. Additionally, by expanding knowledge regarding the specific cellular changes and mechanisms involved post-burn, we will gain a greater understanding of burn-associated immune dysfunction that will enable the development of personalised treatments to improve long-term outcomes for children with burns.

Biography

Dr Barrett is an early-mid career postdoctoral researcher who specialises in molecular genetics, cell biology and immunology. She has been working with the Burn Injury Research Unit for the past 5 years, with a focus on the long-term impact of non-severe burn on the immune system.