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.