CD56+CD57+ natural killer cell infiltration is associated with antibody-mediated rejection in kidney transplantation

Abstract

Natural killer (NK) cells have crucial functions in antibody-mediated rejection (ABMR) and graft failure after kidney transplantation. However, the features and clinical indications of specific subsets of infiltrated NK cells have not been fully evaluated yet. Thirty-nine clinically indicated transplant biopsies performed at Asan Medical Center from May 2015 to July 2017 were analyzed by Opal multiplex immunohistochemistry (IHC). Study groups were classified into three different groups as no rejection (NR) group, T cell-mediated rejection (TCMR) group, and antibody-mediated rejection (ABMR) group according to histopathologic reports; 8 patients (20.5%) belonged to the NR group, 11 (28.2%) to the TCMR group, and 20 (51.3%) to the ABMR group. Paraffin-embedded sections of 39 renal biopsies were labeled using Opal™ multiplex kit (PerkinElmer®). Anti-CD3, anti-CD56, anti-CD57, anti-CD49b, anti-NKG2A, and anti-KIR antibodies were used to define NK cells. NK cells were defined as CD3–CD56+ lymphocytes that are positive for CD57, CD49b, NKG2A, or KIR. Opal™ multiplex IHC revealed that the density of NK cells was significantly higher in the ABMR group (2.57 ± 2.58/mm2) than in the NR (0.12 ± 0.22 /mm2) or the TCMR (0.25 ± 0.34/mm2) group (P = .002). Remarkably, infiltrated CD3-CD56+CD57+ cells (2.16 ± 1.89) were the most frequently detected compared with CD3-CD56+CD49b+ (0.05 ± 0.13), CD3-CD56+NKG2A+ (0.21 ± 0.69), and CD3-CD56+KIR+ (0.15 ± 0.42) cells in the ABMR group (P < .001). Kaplan-Meier survival analysis revealed that death-censored graft failure was significantly higher in recipients with NK cells infiltration compared to those without NK cells infiltration (Log-rank test, p=0.025). In conclusion, infiltrated CD56+CD57+ cells are the main subset of NK cells in kidney transplant recipients with ABMR, and the presence of infiltrated NK cells is associated with graft failure post-transplant.