G.N. de Graav, D.A. Hesselink, W. Verschoor, M. Dieterich, T. van Gelder, W. Weimar, C.C. Baan
Chair(s): dr. Ron W.F. de Bruin, Erasmus MC, Rotterdam
Thursday 10 march 2016
12:30 - 13:00h at Foyer
Parallel session: Postersessies XI - Opgesplitst in 3 tijdblokken en 3 categoriëen (klinisch, basaal, donatie)
Belatacept blocks CD28-mediated T-cell activation by binding CD86 on antigen presenting cells. No therapeutic drug monitoring of serum levels is recommended for belatacept, because of low inter-patient variability in pharmacokinetic parameters. We questioned whether the CD86 competition flow cytometry assay on monocytes and on donor-antigen stimulated B cells could be useful as a tool for pharmacodynamic monitoring of belatacept therapy. CD86-expression was assessed on monocytes and donor-antigen activated B cells of patients treated with tacrolimus or the Less-Intensive regimen of belatacept, in the stable situation and during rejection. Before transplantation, flow cytometric analysis of whole blood samples showed that CD86 was expressed on monocytes: median 2029 molecules/cell [1179-4102]. After one dose of belatacept the numbers of free CD86-molecules per monocyte dropped by >85% in all patients (n=17), p=0.0003. In tacrolimus-treated patients (n=19) the expression levels of this co-stimulatory molecule decreased by 33% (p=0.003), significantly less than in belatacept treated patients (p<0.0001). For the entire one year study period the numbers of free CD86-molecules per monocyte remained stable in patients without rejection treated with either belatacept or tacrolimus. Also during rejection the CD86-expression on monocytes was still blocked for >85% in belatacept-treated patients. CD86 was not detectable on circulating B cells and was subsequently studied in vitro after stimulation with donor antigen in the presence and absence of added belatacept. After stimulation, the CD86-expression on B cells increased to ~40%, and was 55% lower in the presence of therapeutic concentrations of belatacept (10 µg/mL) vs. 38% lower with tacrolimus (10 ng/mL), p=0.02. No significant differences were found between CD86-expression on B cells obtained from rejectors or non-rejectors. The fully effective blockade of CD86 on blood monocytes did not prevent the occurrence of rejection, which makes this assay less suitable for TDM to prevent rejection. Belatacept only partly blocked CD86-expression on in vitro donor-antigen re-activated B cells. Since the magnitude of blockade by belatacept was not different between rejectors and non-rejectors, this assay will not be instrumental in improving efficacy of belatacept treatment.