The clinical significance of the MIF homolog d-dopachrome tautomerase (MIF-2) and its circulating receptor (sCD74) in burn

Abstract

Background We reported earlier that the cytokine macrophage migration inhibitory factor (MIF) is a potential biomarker in burn injury. In the present study, we investigated the clinical significance in severely burned patients of expression levels the newly discovered MIF family member D-dopachrome tautomerase (DDT or MIF-2) and their common soluble receptor CD74 (sCD74). Methods DDT and sCD74 serum levels were measured 20 severely burned patients and 20 controls. Serum levels were correlated to the abbreviated burn severity index (ABSI) and TBSA followed by receiver operating characteristic (ROC) analysis. Data were supported by gene expression dataset analysis of 31 burn patients and 28 healthy controls. Results CD74 and DDT were increased in burn patients. Furthermore, CD74 and DDT also were elevated in septic non-survivors when compared to survivors. Serum levels of DDT showed a positive correlation with the ABSI and TBSA in the early stage after burn injury, and the predictive character of DDT was strongest at 24 hrs. Serum levels of CD74 only correlated with the ABSI five days post-injury. Conclusions DDT may assist in the monitoring of clinical outcome and prediction of sepsis during the early post-burn period. sCD74 and MIF, by contrast, have limited value as an early predictor of death due to their delayed response to burn injury.

Plasma Levels of Macrophage Migration Inhibitory Factor and d-Dopachrome Tautomerase Show a Highly Specific Profile in Early Life

“…This is in line with the observation that MIF levels in tracheal aspirates obtained within the first 2 days of life are reduced in preterm infants who develop BPD (27, 30). Studies on the role of DDT have been limited to adults in humans and animals so far (34–36, 45, 60–62), and we do not known to which extend DDT impacts, like MIF, on lung development and innate immune responses in early life. Interestingly, IL-8 was detected in fetuses and preterm newborns, but not in term infants, children, and adults.…”

“…Blood levels of DDT are elevated in burn, septic, and cancer patients, and during cardiac surgery, and correlate with disease severity and clinical outcome (35–37). DDT, but not MIF, is a valuable biomarker to predict clinical outcome and sepsis occurrence after burn injury (36). So far, circulating levels of DDT in newborns and children have not been reported.…”

Soluble CD74 Reroutes MIF/CXCR4/AKT‐Mediated Survival of Cardiac Myofibroblasts to Necroptosis

“…Ectodomain shedding represents an important posttranslational modification event that downregulates cell‐surface expression of various receptors and liberates biologically active fragments that often exhibit a function that is distinct from that of the membrane‐bound receptor form 38. Although the effects of the intracellular domain of CD74, released following regulated intracellular proteolysis, have been extensively studied,39, 40, 41 we are only beginning to understand the functions of the CD74 ectodomain 37, 39, 42, 43, 44…”

MIF family cytokines in cardiovascular diseases and prospects for precision-based therapeutics

“…A circulating soluble form of CD74 (sCD74) also has been recently identified that appears to form by proteolytic truncation of the MIF binding ectodomain [35]. sCD74 binds MIF and transduces signal activity in vivo, and recent studies have implicated it in the clinical expression of autoimmune liver disease, acute lung injury, burn injury, and postoperative inflammatory responses [35, 36, 37, 38]. …”