The objective of the study is to test whether circulating proteasomes are increased in
burn patients and to assess whether possible alterations are associated with severity of injury, organ failure, and/or clinically relevant outcomes. In this study, plasma was obtained from
burn patients on days 0 (admission, n = 50), 1 (n = 36), 3 (n = 35), 5 (n = 28), 7 (n=34), and 30 (n = 10) (controls: 40 volunteers). The 20S/
26S proteasome levels were measured by
enzyme-linked
immunosorbent assay.
Proteasome peptidase activity was assessed using a chymotryptic-like
peptide substrate in combination with
epoxomicin (specific
proteasome inhibitor). Percentage of TBSA burned, presence of inhalation injury, development of
sepsis/
multiple organ failure, and sequential organ failure assessment scores were documented. On admission, plasma
proteasome activity was higher in patients than in controls (P = .011). 26S proteasomes were not detectable. The
20S proteasome concentrations (median [25th/75th percentile]) peaked on day 0 (673 [399/1566] ng/mL; control: 195 [149/249] ng/mL, P < .001), gradually declined within 7 days, and fully returned to baseline at day 30 (116.5 [78/196] ng/mL). Elevated 20S proteasomes were associated with the presence of inhalation injury and correlated linearly with %TBSA in patients without inhalation injury. Initial
20S proteasome concentrations discriminated the presence of inhalation injury in patients with (sensitivity 0.88 and specificity 0.71) and without (sensitivity 0.83 and specificity 0.97) cutaneous
burns but did not discriminate
sepsis/
multiple organ failure development or survival. Circulating
20S proteasome is a
biomarker of tissue damage. The
20S proteasome plasma concentrations in patients with
burns and/or inhalation injury are unlikely to predict outcomes but may be useful for the diagnosis of inhalation injury.