Objective: To investigate the role of pericyte dysfunction in antibody-mediated rejection (AMR) on the prognosis of transplanted kidneys.
Methods: A total of 160 patients who underwent kidney transplantation in our hospital from 2004 to 2020 were enrolled in this study, divided into 4 groups according to their pathological diagnosis of renal needle biopsies: AMR group (n=79), TCMR group (n=20), mixed group (n=25) and control group (n=36). Indexes concerning postoperative renal function were compared among the four groups, other clinical factors were also analyzed for exploring influential factors affecting the prognosis of allograft. Immunohistochemical staining of 12 samples of patients’ transplanted kidneys from AMR group, TCMR group and control group respectively and immunofluorescence staining of 4 samples from AMR group and control group of kidney transplantation mice models with pericyte markers PDGFR-β and NG2 were performed to compare the difference of expression of pericytes around peritubular capillaries. Western blotting was used to examine the expression of PDGFR-β and NG2 in mice models’ samples.
Results: Among the four groups of transplant patients, there were statistically significant differences in creatinine, urea nitrogen, urine protein and estimated glomerular filtration rate(eGFR) one year, two years, three years, five years hence the transplantation. Patients in AMR group were with the highest creatinine, urea nitrogen and urine protein, the lowest eGFR and the worst prognosis. Univariate analysis showed that pathological diagnosis, DSA, immunotherapy, preoperative renal function, and v, ptc, ci, ct, mm in Banff score were the influencing factors for the prognosis of transplanted kidneys. The immunohistochemistry results showed that the expression of pericytes was all positive in three groups, the expression of pericyte in the AMR group was significantly lower than that in the other two groups by semi-quantitative analysis (P＜0.05). The immunofluorescence staining assays and western blotting of the samples from mice models showed that the expression of PDGFR-β and NG2 was lower in AMR group than in control group (P＜0.05).
Conclusions: Antibody-mediated rejection worsen the prognosis of transplanted kidneys. The results of renal needle biopsy samples showed that the expression of pericytes in the AMR group was remarkably reduced, suggesting that pericyte dysfunction might be the cause of poor prognosis in AMR patients.