Alteration of Transthyretin Microheterogeneity in Serum of Multiple Trauma Patients

Transthyretin (TTR) which exists in various isoforms, is a valid marker for acute phase response and subclinical malnutrition. The aim of the study was to investigate the relationship between inflammation, oxidative stress and the occurrence of changes in microheterogeneity of TTR. A prospective, observational study at a level-I trauma center of a large urban medical university was performed. Patients were severely injured (n = 18; injury severity score (ISS): 34–66), and were observed within the first 24 hours of admittance and over the following days until day 20 after injury. 20 healthy subjects, matched by age and sex, were used as controls. TTR was enriched by immunoprecipitation. Microheterogeneity of TTR was determined by linear matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). Four major mass signals were observed for TTR representing native, S-cysteinylated, S-cysteinglycinylated and S-glutathionylated TTR. In the course of their ICU stay, 14 of the 18 patients showed a transient change in microheterogeneity in favour of the S-cysteinglycinylated form of TTR (p < 0.05 vs. controls). The occurrence of this variant was not associated with the severity of trauma or the intensity of the acute-phase response, but was associated with oxidative stress as evidenced by Trolox. Our results demonstrate that changes in microheterogeneity of TTR occur in a substantial number of ICU trauma patients. The diagnostic values of these changes remains to be elucidated. It is speculated that TTR modification may well be the mechanism underlying the morphological manifestation of amyloidose or Alzheimer’s diseases in patients surviving multiple trauma.