Dendritic Cells as a Non-Invasive Immunological Biomarker of the Late Cellular Rejection after Kidney Transplantation

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Abstract

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.

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