Prediction of lung-transplant rejection by hepatocyte growth factor

Abstract

Graft rejection is a major complication of lung transplantation. No serological marker of rejection is in common use. Hepatocyte growth factor (HGF) is highly expressed in the lung and produced after acute lung injury; serum concentrations increase in inflammatory lung diseases. We investigated whether HGF could be an accurate marker for prediction of lung-graft rejection. Serum concentrations of HGF were measured by ELISA in 109 patients who had undergone lung transplantation (65 for chronic obstructive pulmonary disease; 23 for cystic fibrosis; 21 for idiopathic lung fibrosis), comparing those who had no subsequent events and those with episodes of infection or rejection, as well as in 12 healthy controls. The mean baseline serum HGF concentration was 645 ng/L (SD 259) in controls and 1358 ng/L (603) in the patients before transplantation. After transplantation the mean concentration in patients with no events was 1147 ng/L (510) compared with 1559 ng/L (323) in patients with infection (p=0.001 vs controls; change from pretransplant value not significant). Patients with rejection had significantly higher concentrations than all other groups (3972 ng/L [1463], p<0.0001). Logistic regression identified HGF as a predictor for lung graft rejection (p=0.012). After steroid treatment, HGF concentrations returned almost to the preoperative values within 3 days. HGF might be a marker for graft rejection in lung transplantation. A potential link between viral infection, mainly cytomegalovirus, and HGF, however, remains to be investigated.