Combination of Serum Leucine-rich Alpha-2-Glycoprotein 1 and Citrulline as Biomarkers of Graft Monitoring and Response to Antirejection Treatment in Intestinal Transplantation

BACKGROUND: Intestinal transplantation (ITx) has the highest rejection rate among solid organ transplantations. Nevertheless, convenient, reliable, and noninvasive biomarkers for rejection surveillance are lacking. Leucine-rich alpha-2-glycoprotein 1 (LRG-1) has been developed as a new serum biomarker of disease activity in numerous gastrointestinal inflammatory pathologies. Therefore, this study aimed to evaluate the utility of serum LRG-1 as a biomarker for predicting post-ITx rejection, using citrulline as a known marker. METHODS: Serum LRG-1 (n = 77) and citrulline (n = 64) samples were obtained from 5 post-ITx patients. We analyzed the correlation between these serum levels and the "villi appearance, erythema, capillary network, crypt widening, and heterogeneity (VENCH)" score according to the endoscopic findings of the intestinal graft evaluated on the same day as serum sample collection, as well as histopathological diagnosis. RESULTS: We observed a negative correlation between serum LRG-1 and citrulline levels. LRG-1 values in the VENCH score ≥4 group were significantly higher than those in the VENCH <4 group (P < 0.0001). The area under the curve of the citrulline/LRG-1 (C/L) ratio for detecting endoscopic abnormalities was 0.896 (sensitivity: 0.87; specificity: 0.89). In addition, LRG-1 values in the pathological rejection group were significantly higher than those in the nonrejection group (P < 0.0001). The area under the curve of the C/L ratio for detecting rejection was 0.992 (sensitivity: 1.0; specificity: 0.94). CONCLUSIONS: The present data support the hypothesis that LRG-1 is an attractive noninvasive biomarker of rejection after ITx, especially as an indicator, such as the C/L ratio. Routine serum LRG-1 monitoring may help to reduce the frequency of invasive endoscopic surveillance.