Immunity & Ageing (Dec 2022)

Investigating the potential of a prematurely aged immune phenotype in severely injured patients as predictor of risk of sepsis

  • Mark A. Foster,
  • Conor Bentley,
  • Jon Hazeldine,
  • Animesh Acharjee,
  • Ornit Nahman,
  • Shai S. Shen-Orr,
  • Janet M. Lord,
  • Niharika A. Duggal

DOI
https://doi.org/10.1186/s12979-022-00317-5
Journal volume & issue
Vol. 19, no. 1
pp. 1 – 16

Abstract

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Abstract Background Traumatic injury elicits a hyperinflammatory response and remodelling of the immune system leading to immuneparesis. This study aimed to evaluate whether traumatic injury results in a state of prematurely aged immune phenotype to relate this to clinical outcomes and a greater risk of developing additional morbidities post-injury. Methods and findings Blood samples were collected from 57 critically injured patients with a mean Injury Severity Score (ISS) of 26 (range 15–75 years), mean age of 39.67 years (range 20–84 years), and 80.7% males, at days 3, 14, 28 and 60 post-hospital admission. 55 healthy controls (HC), mean age 40.57 years (range 20–85 years), 89.7% males were also recruited. The phenotype and frequency of adaptive immune cells were used to calculate the IMM-AGE score, an indicator of the degree of phenotypic ageing of the immune system. IMM-AGE was elevated in trauma patients at an early timepoint (day 3) in comparison with healthy controls (p < 0.001), driven by an increase in senescent CD8 T cells (p < 0.0001), memory CD8 T cells (p < 0.0001) and regulatory T cells (p < 0.0001) and a reduction in naïve CD8 T cells (p < 0.001) and overall T cell lymphopenia (p < 0 .0001). These changes persisted to day 60. Furthermore, the IMM-AGE scores were significantly higher in trauma patients (mean score 0.72) that developed sepsis (p = 0.05) in comparison with those (mean score 0.61) that did not. Conclusions The profoundly altered peripheral adaptive immune compartment after critical injury can be used as a potential biomarker to identify individuals at a high risk of developing sepsis and this state of prematurely aged immune phenotype in biologically young individuals persists for up to two months post-hospitalisation, compromising the host immune response to infections. Reversing this aged immune system is likely to have a beneficial impact on short- and longer-term outcomes of trauma survivors.

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