Abstract
Previous studies have implicated the role of CD146 and its soluble form (sCD146) in the pathogenesis of inflammatory diseases. However, the association between CD146 and acute rejection in kidney transplant patients remains unexplored. In this study, fifty-six patients with biopsy-proved rejection or non-rejection and 11 stable allograft function patients were retrospectively analyzed. Soluble CD146 in plasma was detected in peripheral blood by enzyme linked immunosorbent assay (ELISA), and local CD146 expression in graft biopsy was detected by immunohistochemistry. We found that plasma soluble CD146 in acute rejection recipients was significantly higher than in stable patients without rejection, and the biopsy CD146 staining in the rejection group was higher than that of the non-rejection group. Multivariate analysis demonstrated soluble CD146 as an independent risk factor of acute rejection. The area under the receiver operating characteristic curve (AUC) of sCD146 for AR diagnosis was 0.895, and the optimal cut-off value was 75.64 ng/ml, with a sensitivity of 87.8% and a specificity of 80.8%, which was better than eGFR alone (P = 0.02496). Immunohistochemistry showed CD146 expression in glomeruli was positively correlated with the Banff-g score, and its expression in tubules also had a positive relationship with the Banff-t score. Therefore, soluble CD146 may be a potential biomarker of acute rejection. Increased CD146 expression in the endothelial or tubular epithelial cells may imply that endothelial/epithelial dysfunction is involved in the pathogenesis of immune injury.
Highlights
Kidney transplantation is a preferred treatment for patients with end stage renal disease (ESRD), improving quality of life and survival more so than dialysis [1]
The results of this study suggest that plasma sCD146 level may be useful for monitoring acute rejection in renal transplant recipients, and sCD146 might function as a pro-inflammatory marker which facilitates the development of rejection
Prior studies have shown that CD146 and its soluble form are associated with endothelial dysfunction or injury and play a crucial role in inflammatory diseases
Summary
Kidney transplantation is a preferred treatment for patients with end stage renal disease (ESRD), improving quality of life and survival more so than dialysis [1]. We hypothesize circulating sCD146 or CD146 expression in renal allografts increases in kidney transplant patients with acute rejection. Plasma sCD146 and CD146 expression in allograft biopsies of renal transplant recipients were examined to evaluate the capability of sCD146 as a less invasive biomarker of acute rejection. We enrolled 11 renal transplant patients from a surveillance program after kidney transplantation, who visited the outpatient clinic of our center at the same period, as a control group reflecting postoperative normal state These controls had a stable allograft function, and no history of kidney diseases, diabetes, cardiovascular events, or autoimmune disorders. All statistical analyses were performed using GraphPad Prism (v.7.04) and R software (v.2.10.1)
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