Dendritic Cells as a Non-Invasive Immunological Biomarker of the Late Cellular Rejection after Kidney Transplantation.
Sergey Korotkov1, Alexandr Nosik1, Victoria Smolnikova1, Victoria Grinevich1, Margarita Dmitrieva1, Aleksei Siantovich1, Oleg Yudina1, Denis Efimov1, Aleksei Fedoruk1, Aleksei Shcherba1, Oleg Kalachik1, Svetlana Krivenko1, Oleg Rummo1.
1Belorussian Republican Center of Organ and Tissue Transplantation, Minsk, Belarus
The Aim of the Study was to determine the association between peripheral blood leukocytes subpopulations and late immunological kidney transplant dysfunction.
Materials and Methods: This is a report of retrospective single center case-control study involving 44 patients who underwent kidney transplantation. Inclusion criteria: adult kidney transplant recipients who received first kidney transplant with a follow-up 4 and more years after KT. Exclusion criteria were infectious and oncological complications in the postoperative period, high immunological risks at the time of surgery (HLA mismatching, PRA>15%). First group (REJ) include 22 patients with chronic graft dysfunction, caused by biopsy proven late cellular rejection. Second group (STA) contained of 22 recipients, who haven’t any dysfunction in posttransplant period. Flow cytometry of peripheral blood cells was performed for establishment of immunophenotyping markers of late cellular rejection after kidney transplantation.
Results:The level of dendritic cells (DC) subsets significantly differed in study groups. Myeloid DCs were significantly lower in participants (REJ) with late cellular rejection than in stable recipients (STA): 0,65% (0,36-0,73) vs 1,05% (0,67-1,4), respectively (p<0,01). Absolute counts of cells were 0,039 (0,028-0,056) x109/l vs 0,063 (0,049-0,076) x109/l respectively for REJ and STA groups (p=0,003). Plasmacytoid DCs were significantly lower in participants with late cellular rejection too: 0,055% (0,04-0,085) vs 0,09% (0,05-0,12), REJ vs STA respectively (p=0,02). Absolute counts of pDC were 0,0038 (0,0021-0,0054) x109/l vs 0,005 (0,0035-0,007) x109/l in REJ and STA groups (p=0,041) Diagnostic value of each marker was assessed by receiver operating characteristic analysis. Optimal cut-off of myeloid DC, which can accurately discriminate late cellular rejection, was assessed as 0.87%, with area under ROC curve (AUC) 0.784, sensitivity 86.36%, and specificity 63.64%. For plasmacytoid DC optimal cut-off was 0.085%, with AUC 0.7, sensitivity 77.72%, and specificity 59%. Odds ratio of DC subsets frequency mitigation at time of late kidney rejection was 11.08 (p<0.01) for myeloid DC, and 4.91 (p=0.017) for plasmacytoid DC respectively.
Conclusion: The results of the study showed that the level of circulating myeloid and plasmacytoid dendritic cells can be effective non-invasive immunological marker of late cellular rejection after kidney transplantation.
