Treatment of antibody-mediated rejection (AMR) in renal transplant (Tx) patients (pts) is still challenging and long-term outcome remain poor. Our present treatment strategy with bortezomib (BZ) and rituximab (Rmab) display a synergistic approach targeting precursor and mature HLA antibody (DSA) producing plasma blasts (PB) and plasma cells (PC). The aim of this study was to investigate the impact of this combined therapy on different B-cell subsets inclusive PC and PB in a prospective long-term approach over 2 years.

AMR therapy was introduced in 10 Tx pts with DSA and biopsy proven AMR according to BANFF classification. Therapy included steroid pulse, PPH (6x), BZ (1.3.mg/m2; one cycle), 500mg Rmab and IVIG 1.5g/kg). Phenotype of PCs (CD19dimCD27+CD38+HLA-DRneg) and PBs (CD19dimCD27+CD38+HLA-DR+) were characterized by flow cytometry at baseline (BL), month (M) 1, 3, 6, 12, 18 and 24. DSA MFI were evaluated with Luminex technique.

1M after treatment PC and PB count were significantly lower compared to BL (mean: 0.06±0.01 vs. 1.3±0.3/[micro]l; p=0.001) respectively. Effects were still evident 12 and 24M post treatment (0.11±0.1 and 0.23±0.15/[micro]l; p<0.01). Interestingly, relatively more PBs were detectable in contrast to PCs, already 1 M after treatment (4.1% vs. 1.7% of B-cells; p<0.05). PBs were the predominant subset in this subpopulation over the complete follow up of 24M (PB: 1.2% vs. PC:0.4%; p<0.05).

CD19B-cells were depleted sustainable (BL: 161.4/[micro]l; M1:0.9/[micro]l; M24: 7.4/[micro]l; p<0.01). CD20CD27+ memory B-cells are the most frequent recovering population in contrast to naïve B-cells. Memory B-cells recovered within 12M completely, whereas naïve B-cells were still affected 24M post treatment.

MFI of DSAmax were reduced 3M after therapy compared to baseline (MFI:2500±2453 vs. 4865±2082; p=0.018). 1 year post treatment DSAmax recovered back to baseline.

The present study observed a sustained reduction of peripheral PCs, PBs and B-cells after a combined AMR therapy with BZ + Rmab. However, PBs and memory B-cells are the predominant B-cell subsets that recovered completely within 12M. Interestingly, beside these cell reductions in the periphery, MFI of DSAmax were affected only short-term. Thus, the effect of BZ and Rmab on tissue-based long-lived PCs may be limited. This present data may be helpful in the understanding of B-cell biology in context of AMR.

CITATION INFORMATION: Duerr M, Halleck F, Staeck O, Lehner L, Khadzhynov D, Eva S, Waiser J, Budde K. Prospective Long-Term Analysis of B- and Plasma Cell Subsets in Renal Transplant Patients After Combined Treatment with Rituximab and Bortezomib in Antibody Mediated Rejection. Am J Transplant. 2016;16 (suppl 3).

« Back to 2016 American Transplant Congress