Effector memory CD4+ T-cells and dendritic cells are noninvasive biomarkers of late cellular rejection after kidney transplantation

Introduction. Diagnosis of the kidney transplant cellular rejection in the long-term after transplantation remains a challenge. Usual surrogate markers are not enough sensitive and specific. Rejection is an immune reaction to donor alloantigens. The kidney transplant biopsy to diagnose a dysfunction is an invasive procedure with the incidence of complications about 12.6% and can lead to transplant loss. In this regard, the search of immunological biomarkers for early noninvasive and accurate diagnosis of kidney transplant rejection is an actual task.

Material and methods. This is a report of the observational retrospective single-center, comparative case-control study in two groups involving 44 patients who underwent kidney transplantation. The first group (REJ) included the patients with the chronic graft dysfunction caused by a biopsy-confirmed late cellular rejection (22 patients). The second group (STA) included the recipients who had no dysfunction in the posttransplant period (22 patients). Flow cytometry of peripheral blood cells was performed to identify immunophenotyping markers of late cellular rejection after kidney transplantation (we determined subpopulations of T, B lymphocytes, and dendritic cells).

Results. As a result of our work, we found significant differences in the absolute count of effector memory T cells making 0.147 (0.115–0.260) × 10⁹ cell/L in REJ group, and 0.106 (0.067–0.136) × 10⁹ cell/L in STA group (р = 0.0167).  Relative and absolute counts of myeloid dendritic cells were also different between the groups: 0.65 (0.36–0.73) vs. 1.05 (0.67–1.4) % and 0.039 (0.028–0.056) vs. 0.063 (0.049–0.076) × 10⁹ cell/L, respectively (р = 0.0009, р = 0.003). The numbers of plasmacytoid dendritic cells were also different between the study groups: 0.0038 (0.0021–0.0054) vs. 0.005 (0.0035–0.007) × 10⁹ cell/L for an absolute count (р = 0.0414), and 0.055 (0.04–0.085) vs. 0.09 (0.05–0.12) % for a relative count (р = 0.0197).

Conclusion. The obtained data showed that the blood level of dendritic cells, which are the main “professional” initiators of immune reaction, and the level of effector helper T memory cells, which constitute the main lymphocyte subpopulation posing a destructive impact on the kidney transplant, can be considered as diagnostic markers of kidney transplant cellular rejection in the long-term after surgery.

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