The impact of belatacept on third-party HLA alloantibodies in highly sensitized kidney transplant recipients

Abstract

Recent evidence suggests that belatacept reduces the durability of preexisting antibodies to class I and class II human leukocyte antigens (HLAs). In this case series of 163 highly sensitized kidney transplant candidates whose calculated panel-reactive antibody (cPRA) activity was ≥98% to 100%, the impact of belatacept on preexisting HLA antibodies was assessed. Of the 163 candidates, 72 underwent transplantation between December 4, 2014 and April 15, 2017; 60 of these transplanted patients remained on belatacept consecutively for at least 6 months. We observed a decrease in the breadth and/or strength of HLA class I antibodies as assessed by FlowPRA in belatacept-treated patients compared to controls who did not receive belatacept. Specifically, significant HLA antibody reduction was evident for class I (P < .0009). Posttransplant belatacept-treated patients also had a clinically significant reduction in their cPRA compared to controls (P < .01). Collectively, these findings suggest belatacept can reduce HLA class I antibodies in a significant proportion of highly sensitized recipients and could be an option to improve pretransplant compatibility with organ donors.

Keywords: alloantibody; clinical research/practice; immunosuppressant - fusion proteins and monoclonal antibodies: belatacept; immunosuppression/immune modulation; kidney transplantation/nephrology; sensitization.

Figure 1:. A schematic representation distinguishing patients treated with belatacept from patients treated with control immunosuppression.

*= FlowPRA analysis was performed separately for class I and class II antibodies. For each class, a FlowPRA value >20% was required for patient inclusion.^**cPRA values from predicated on their pre-transplant FlowPRA (class I and class II) being >20%.

Figure 2:. Graphic illustration of treatment regimens for patients treated with belatacept vs control immunosuppression.

Figure 3:. FlowPRA® Histograms in belatacept-treated highly sensitized recipients versus recipients treated with control immunosuppression.

Class I and II FlowPRA® histograms comparing six highly sensitized kidney transplant recipients pre- and post-transplant, who were received either receiving control immunosuppression or a regimen that included belatacept. The patients that are shown represent the spectrum of response to Belatacept: change in both fluorescence intensity and architecture (D), peak loss with minor change in fluorescence intensity (E) and change in fluorescence intensity with minor change in peak architecture.

Figure 4:. Comparison of changes in FlowPRA® for Class I & II for highly sensitized recipients treated with either control immunosuppression or belatacept.

The percent change in class I & II FlowPRA ® values for the control immunosuppression patients (n=33 & 32 for Class I & II, respectively) and the belatacept-treated recipients (n=59 & 49 for Class I & II, respectively). Dots represent individual patients and their percent FlowPRA® change comparing an immediately pre-transplant sample to a sample obtained post-transplant.

Figure 5:. Post-transplant cPRA values in belatacept-treated highly sensitized recipients (n=60) vs patients treated with control immunosuppression (n=19).

After identifying HLA class I/class II antibodies that had MFI values ≥2000, the corresponding antigens were entered into the UNOS cPRA calculator and cPRA values were derived.