Bootcongres

Introduction. A variety of data indicates a role for B cells in acute renal allograft rejection. We report the type of biopsy proven acute rejection (BPAR) and biopsy findings after induction therapy with a single dose of the anti-B cell antibody rituximab. Patients and methods. In a single centre, double-blind, placebo-controlled study, 280 adult renal transplant patients were randomised between a single dose of rituximab (375 mg/m2) or placebo during transplant surgery. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil, and steroids. The primary end point was the incidence of BPAR within six months after transplantation. Biopsies were scored independently by two blinded pathologists according to the updated Banff 07 criteria. Additionally, biopsies were scored for the B cell markers CD20 (positive when >10% of the cells within infiltrates were CD20+) and CD79a (scored on an ordinal scale from 0-5), the plasma cell marker CD138 (number of cells/HPF), and deposition of C4d. Protocol graft biopsies were not performed. Results. The incidence of BPAR was comparable between rituximab-treated (23/138, 16.7%) and placebo-treated patients (30/142, 21.2%, p=0.25 by log-rank test). Most rejections were predominantly T cell mediated according to the Banff classification. Rituximab-treated patients tended to have less antibody mediated rejections (ABMR), compared to placebo-treated patients (4/138, 2.9% vs. 11/142, 7.7% p=0.11). An additional analysis of biopsies performed during the first six months after transplantation showed that biopsies of rituximab-treated patients were less often CD20+ (18.5% vs 82.9%, p<0.01) , had a lower score for CD79a staining (0.15 vs 1.56, p<0.01), and tended to have less C4d deposition (8.2% vs. 15.8% positive biopsies, p=0.13), compared with biopsies from placebo-treated patients. There was no difference in the number of CD138+ cells (0.35 vs 0.48 per HPF, p=0.43).

Conclusion. The results of our study suggest that a single dose of rituximab may reduce the incidence of ABMR . This is accompanied by a decrease in the number of graft infiltrating B-cells.