Kidney Week

Abstract: SA-PO1149

Phenotype of CD8 T Cells in Determining Risk of Acute Rejection in Kidney Transplant on Belatacept Regimen

Session Information

• Transplantation: Clinical - Rejection, Recurrent Disease, Incompatibility
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 1902 Transplantation: Clinical

Authors

• Shoji, Jun, University of California San Francisco, San Francisco, California, United States

Jun Shoji,

• Vincenti, Flavio, University of California San Francisco, San Francisco, California, United States

Flavio Vincenti,

Background

Belatacept is a costimulatory blocker that is used as de novo maintenance immunosuppression in kidney transplantation. However, patients maintained on belatacept, mycophenolate, and corticosteroids have been noted to have more frequent and severe acute rejection than in calcineurin inhibitors. Experimental studies have shown synergy between costimulatory blockade and mTOR inhibitors. We investigated pretransplant recipient immune profiles to determine which subset of lymphocytes can predict acute rejection in patient on belatacept-based regimen.

Methods

We prospectively enrolled 65 kidney transplant recipients (31 deceased; 34 living donors) at our center to receive denovo belatacept from September 2012 to June 2018. PBMCs were collected prior to transplantation and at the time of biopsies. All patients received thymoglobulin for induction (3mg/kg divided into 2 doses) with belatacept 10mg/kg administered on POD 1, 4, 14, 28, 56, and 84. Monthly maintenance dose of 5mg/kg was given starting week 16. Patients were started initially on MPA but were converted to everolimus after 1 month, and all patients were maintained on prednisone.

Results

16.9% developed acute rejection within the first year post transplant: 2 with ACR 1a, 1 with ACR 2a, 6 with ACR 2b, 1 with AMR, and 1 with simultaneous ACR 1a and AMR. All 11 rejections occurred in those who were on MPA and not on mTORi. 12 patients were found to have borderline rejection on protocol biopsies (7 on mTORi, 5 on MPA). 42 patients did not have any inflammation on biopsies. 57 patients remained on belatacept, and 8 were converted to tacrolimus. Patients who had biopsy-proven rejection or borderline changes had significantly higher %CD8⁺CD28^-T cells, and those who had rejection with low %CD8+CD28- were found to have high CD2^hiCD28^hiin CD8+CD45RO+ T cells. Belatacept patients receiving everolimus had more stable TIGIT expression on regulatory T cells.

Conclusion

This trial of combining belatacept with mTORi shows that it is possible to reduce the rate of acute rejection in belatacept-based regimens. The synergy between mTORi and belatacept may be related to mTORi’s inhibitory effect on memory CD8+CD28-CD38+ cells that are refractory to costimulatory blockade. Pretransplant immunotyping to identify those with low percentage of CD8+CD28- & CD2^hiCD28^hiin CD8+CD45RO+ may reduce the risk of rejection on belatacept.