Increase in Proinflammatory CD14++CD16+ Monocytes in Samples from Aspiration Cytology Compared with Peripheral Blood in Kidney Transplant Patients with Borderline Rejection

Abstract

Introduction Monocytes comprise a heterogeneous population divided according to the membrane expression level of their molecules. One of these populations is the CD14++CD16+, which presents proinflammatory characteristics. Our aim was to evaluate the role of this monocyte population in renal transplant recipients with borderline rejection. Material and Methods This controlled clinical trial (NCT02284464) recruited patients with a low immunological risk to randomly receive conventional triple therapy (steroids, TAC and MMF) versus steroid withdrawal three months after the protocol biopsy. We analysed 66 patients with either a normal histology or borderline rejection. In all the patients we studied pre-randomisation levels of CD14++CD16+ at the third month in peripheral blood (PB) and blood extracted from the graft by fine needle aspiration cytology (FNAP). The monocytes were analysed by flow cytometry using CD14 and CD16 monoclonal antibodies. Results Of the 66 patients, 38 (51.1±12.8 years; 68.4% men) had a normal biopsy and 28 (57.8±9.5 years; 67.9% men) had borderline rejection. The percentage of proinflammatory monocytes was similar in the PB and FNAP samples from the patients with a normal biopsy (PB: 13.2±12.9 vs FNAP:16.3±14.3%; p=0.070). However, in the group with borderline rejection the difference in the percentage of these monocytes was significantly greater in the FNAP sample compared to the PB sample (PB: 7.9±5.4 vs FNAP: 16.9±16.5%; p=0.006). No differences were seen at the time of biopsy in renal function or proteinuria (Normal: Cr=1.6±0.6 vs Borderline: 1.7±0.5 mg/dL; p=0.536 and Normal: 268.2±197.9 vs Borderline: 269.3±239.8 mg/24h; p=0.986). Conclusion These preliminary results show that patients with a diagnosis of borderline rejection in the protocol biopsy present a significant difference in CD14++CD16+ monocytes between peripheral blood and graft blood, despite having a stable renal function. This suggests recruitment of these proinflammatory monocytes. Spanish Ministry of Economy and Competitiveness (MINECO) (grant ICI14/00016) from the Instituto de Salud Carlos III co-funded by the Fondo Europeo de Desarrollo Regional-FEDER, RETICS (REDINREN RD16/0009/0006).