Analysis of CCR4high CD4+ in Kidney Graft Blood after Steroid Withdrawal: A Prospective, Randomized, Controlled, Parallel Group Study. Preliminary Results
Teresa Vazquez1, Abelardo Caballero2, Elisea Marques1, Pedro Ruiz Esteban1, Eulalia Palma1, Juana Alonso-Titos1, Veronica Lopez1, Eugenia Sola1, Mercedes Cabello1, Ana Duarte1, Cristina Jironda1, Domingo Hernandez1.
1Nephrology Department, Regional University Hospital of Malaga and University of Malaga, IBIMA, REDinREN (RD16/0009/0006), Malaga, Spain; 2Immunology Department, Regional University Hospital of Malaga and University of Malaga. IBIMA. REDINREN (RD16/0009/0006), Malaga, Spain
Introduction: Steroids represent a mainstay of immunosuppression after kidney transplant. The infiltration into the graft of active T cells following KT depends on the expression of chemokines and their interaction with their T-cell receptors. However, the natural history of the expression of these molecules in patients who undergo steroid withdrawal after transplant is unknown.
Materials and Methods: In a controlled clinical trial (NCT02284464), a total of 176 KT patients with low immunological risk were recruited to randomly receive either conventional triple immunosuppression: steroids, TAC and MMF (Group A) versus steroid withdrawal at the 3 post-KT month (Group B). We compared the evolution of CCR4highCD4+ and CXCR3highCD4+ lymphocyte subpopulations in graft blood (GB) extracted by fine needle aspiration puncture determined by flow cytometry in patients after steroid withdrawal at the 3 month post-KT versus patients who continue to receive conventional triple immunosuppression. Measurements were made at 3 (baseline) and 6 months post-KT in GB and in peripheral blood (PB).
Results: So far, 68 patients have been randomized (34 in each group). There were no significant differences in the clinical and demographic characteristics between the groups at baseline. The first analysis (at 3 months) in those patients who had completed 6 months of follow-up (Group A: n=13; Group B: n=15) showed a significant increase in the CCR4highCD4 subpopulations in GB versus PB in both groups. However, at six months a significant increase in GB versus PB was only seen in Group A. There were no significant differences in the CXCR3highCD4+ lymphocyte subpopulation at the third or sixth month between GB and PB in either group (Table).
Conclusion: These preliminary results could suggest a possible effect of prednisone that would favor the recruitment of CCR4highCD4+ cells into the renal graft.
Group A | Group B | |||||
PB | GB | P | PB | GB | P | |
CCR4highCD4+ (%) | ||||||
3 months | 0.40±0.34 | 2.28±2.46 | 0.001 | 0.45±0.64 | 2.09±3.84 | 0.003 |
6 months | 0.42±0.57 | 2.97±5.35 | 0.023 | 0.71±0.81 | 1.27±1.43 | 0.117 |
CXCR3highCD4+ (%) | ||||||
3 months | 0.78±1.54 | 0.82±1.30 | 0.950 | 0.72±1.34 | 0.50±0.92 | 0.567 |
6 months | 0.99±1.73 | 1.63±4.64 | 0.423 | 2.82±4.70 | 1.05±1.55 | 0.063 |
Spanish Ministry of Economy and Competitiveness (MINECO) (grant ICI14/00016) from the Instituto de Salud Carlos III co-funded by the Fondo Europeo de Desarrollo Regional–FEDER, RETICS (REDINREN RD12/0021/0015, RD16/0009/0006).