Plasmatic isoforms of cytokeratin 18 and RAGE after severe trauma: a longitudinal cohort study.

Abstract

Life-threatening traumatic injuries lead to a complex inflammation-driven pathophysiology. Receptor of advanced glycation end product (RAGE) is a multiligand receptor of several endogenous alarmins, while cytokeratin 18 is a structural component of the filament of epithelial cells. Both proteins can be frequently found in plasma of patients with different diseases, whereby they have distinct underlying mechanism of formation. In this prospective observational study, we wanted to shed light on the kinetic of plasmatic RAGE and cytokeratin 18 isoforms after severe trauma, thereby also addressing the association of these markers with inflammation and their potential use as biomarkers. Plasma samples of 77 patients with severe multiple trauma as defined by an Injury Severity Score (ISS) 16 or greater were obtained from a local repository and levels of soluble RAGE, endogenous secretory RAGE, cytokeratin 18, cleaved cytokeratin 18, and interleukin 6 by enzyme-linked immunosorbent assay. Demographic and routine parameters of the cohort were extracted from an electronic patient data management system. Both RAGE isoforms were transiently increased in plasma within 24 hours after trauma, while cytokeratin 18 levels were unchanged. Moreover, soluble RAGE concentrations in patients with thoracic injuries were higher compared with patients without injury, and both isoforms of RAGE discriminated between patients with most severe adult respiratory distress syndrome and patients with milder forms. In addition, cleaved and total cytokeratin 18 levels differ between patients with hepatic dysfunction and normal function, without possessing discriminatory power. RAGE and cytokeratin 18 isoforms correlated significantly but to a low extent with interleukin 6, while the isoforms of both parameters correlated to a high extent with one another. The release of RAGE (but not cytokeratin 18) isoforms occurs early and transiently after trauma and is associated with the extent of injury and inflammatory response. RAGE and cytokeratin 18 isoforms have the potential to act as diagnostic or prognostic biomarkers of lung and hepatic dysfunction. Epidemiologic/prognostic study, level IV.