New-onset autoantibodies to selenoprotein P following severe burn injury.

The liver-derived selenium (Se) transporter selenoprotein P (SELENOP) declines in critical illness as a negative acute phase reactant and has recently been identified as an autoantigen. Hepatic selenoprotein biosynthesis and cotranslational selenocysteine insertion are sensitive to inflammation, therapeutic drugs, Se deficiency, and other modifiers. As severe burn injury induces a heavy inflammatory burden with concomitant Se depletion, we hypothesized an impairment of selenoprotein biosynthesis in the acute post-burn phase, potentially triggering the development of autoantibodies to SELENOP (SELENOP-aAb). To test this hypothesis, longitudinal serum samples from severely burned patients were analyzed over a period of six months. Newly occurring SELENOP-aAb were detected in 8.4% (7/83) of the burn patients, with onset not earlier than two weeks after injury. Prevalence of SELENOP-aAb was associated with injury severity, as aAb-positive patients have suffered more severe burns than their aAb-negative counterparts (median [IQR] ABSI: 11 [7-12] vs. 7 [5.8-8], p = 0.023). Autoimmunity to SELENOP was not associated with differences in total serum Se or SELENOP concentrations. A positive correlation of kidney-derived glutathione peroxidase (GPx3) with serum SELENOP was not present in the patients with SELENOP-aAb, who showed delayed normalization of GPx3 activity post-burn. Overall, the data suggest that SELENOP-aAb emerge after severe injury in a subset of patients and have antagonistic effects on Se transport. The nature of burn injury as a sudden event allowed a time-resolved analysis of a direct trigger for new-onset SELENOP-aAb, which may be relevant for severely affected patients requiring intensified acute and long-term care.

Serum Selenium-Binding Protein 1 (SELENBP1) in Burn Injury: A Potential Biomarker of Disease Severity and Clinical Course.

Oxidative stress, systemic inflammation, and metabolic derangements are hallmarks of burn pathophysiology. Severely burned patients are highly susceptible to infectious complications. Selenium-binding protein 1 (SELENBP1) modulates intracellular redox homeostasis, and elevated serum concentrations have been associated with adverse clinical outcomes in trauma patients. We hypothesized that serum SELENBP1 at hospital admission and during hospitalization may constitute a meaningful biomarker of disease severity and the clinical course in burn injury, with pulmonary infection as primary endpoint. To this end, we conducted a prospective cohort study that included 90 adult patients admitted to the Burn Center of the University Hospital Zurich, Switzerland. Patients were treated according to the local standard of care, with high-dose selenium supplementation during the first week. Serum SELENBP1 was determined at nine time-points up to six months postburn and the data were correlated to clinical parameters. SELENBP1 was initially elevated and rapidly declined within the first day. Baseline SELENBP1 levels correlated positively with the Abbreviated Burn Severity Index (ABSI) (R = 0.408; p < 0.0001). In multiple logistic regression, a higher ABSI was significantly associated with increased pulmonary infection risk (OR, 14.4; 95% CI, 3.2-88.8; p = 0.001). Similarly, baseline SELENBP1 levels constituted a novel but less accurate predictor of pulmonary infection risk (OR, 2.5; 95% CI, 0.7-8.9; p = 0.164). Further studies are needed to explore the additional value of serum SELENBP1 when stratifying patients with respect to the clinical course following major burns and, potentially, for monitoring therapeutic measures aimed at reducing tissue damage and oxidative stress.