Pretransplant Numbers of CD16+ Monocytes as a Novel Biomarker to Predict Acute Rejection after Kidney Transplantation

Abstract

Acute rejection is one of the major immunological determinants of kidney graft function and survival. Early biomarkers to predict rejection are lacking. Emerging evidence reveals a crucial role for the monocyte-macrophage lineage cells in the pathogenesis of rejection. We hypothesized that higher pre-transplant numbers of proinflammatory CD16+ monocytes can predict rejection. The study cohort consisted of 104 kidney transplant recipients (58 non-rejectors and 46 biopsy-proven rejectors), and 33 healthy individuals. Posttransplant median ± IQR follow up time was 14.7 (0.3-34) months. Pretransplantation blood samples were analyzed by flow cytometry for monocyte immunophenotypes. Groups were compared by Cox regression models for the occurrence of acute rejection. We documented a significantly increased absolute number of pretransplant CD16+ monocytes in patients who developed biopsy proven rejection after transplantation compared to non-rejectors and healthy individuals (Hazard Ratio [HR], 1.60; 95% Confidential Interval [CI], 1.28 to 2.00; p < 0,001 and HR, 1.47; CI, 1.18 to 1.82, p < 0,001). In parallel, significantly less absolute numbers of CD16- monocytes were observed at pretransplant time point in rejectors vs non-rejectors (HR, 0.74; CI, 0.58 to 0.94; p < 0,014). A higher pre-transplant number of CD16+ monocytes is significantly associated with a higher risk of acute rejection after kidney transplantation.