TY - JOUR
T1 - Absence of Intragraft B Cells in Rejection Biopsies After Rituximab Induction Therapy: Consequences for Clinical Outcome
AU - van den Hoogen, Martijn W. F.
AU - Steenbergen, Eric J.
AU - Baas, Marije C.
AU - Florquin, Sandrine
AU - Hilbrands, Luuk B.
PY - 2017
Y1 - 2017
N2 - Background. The pathophysiological role of intragraft B cells during renal allograft rejection is unclear. Methods. We studied B-cell infiltration during acute rejection in 53 patients who participated in a clinical trial in which adult renal transplant patients were randomized between a single intraoperative dose of rituximab (375 mg/m(2)) or placebo as induction therapy. Two independent pathologists scored all biopsies in a blinded fashion according to the Banff classification and scored for the presence of B cells and plasma cells using CD79a and CD138 as markers. Results. The majority of acute rejections were T cell-mediated. The proportion of acute rejections with an antibody-mediated component tended to be lower in rituximab-treated patients (4/23, 17.4%) than in placebo-treated patients (11/30, 36.7%; P = 0.14). Biopsies of rituximab-treated patients had significantly lower scores for B cells (0.00; range, 0.00-0.50 vs 1.70; range, 0.60-3.30; P <0.0001) and plasma cells (0.10; range, 0.00-1.90 vs 0.40; range, 0.00-7.50; P = 0.006). During acute rejection, intragraft clusters of B cells were not observed after rituximab induction therapy. However, the depletion of intragraft B cells during acute rejection did not affect steroid resistance, proteinuria, graft function at 2 years follow-up, or patient and graft survival at a median follow-up of 4.1 years (range, 2.0-6.2 years). Conclusions. These data do not support a harmful influence of intragraft B cells present during acute allograft rejection on the clinical course within the first few years after renal transplantation
AB - Background. The pathophysiological role of intragraft B cells during renal allograft rejection is unclear. Methods. We studied B-cell infiltration during acute rejection in 53 patients who participated in a clinical trial in which adult renal transplant patients were randomized between a single intraoperative dose of rituximab (375 mg/m(2)) or placebo as induction therapy. Two independent pathologists scored all biopsies in a blinded fashion according to the Banff classification and scored for the presence of B cells and plasma cells using CD79a and CD138 as markers. Results. The majority of acute rejections were T cell-mediated. The proportion of acute rejections with an antibody-mediated component tended to be lower in rituximab-treated patients (4/23, 17.4%) than in placebo-treated patients (11/30, 36.7%; P = 0.14). Biopsies of rituximab-treated patients had significantly lower scores for B cells (0.00; range, 0.00-0.50 vs 1.70; range, 0.60-3.30; P <0.0001) and plasma cells (0.10; range, 0.00-1.90 vs 0.40; range, 0.00-7.50; P = 0.006). During acute rejection, intragraft clusters of B cells were not observed after rituximab induction therapy. However, the depletion of intragraft B cells during acute rejection did not affect steroid resistance, proteinuria, graft function at 2 years follow-up, or patient and graft survival at a median follow-up of 4.1 years (range, 2.0-6.2 years). Conclusions. These data do not support a harmful influence of intragraft B cells present during acute allograft rejection on the clinical course within the first few years after renal transplantation
U2 - https://doi.org/10.1097/TXD.0000000000000659
DO - https://doi.org/10.1097/TXD.0000000000000659
M3 - Article
C2 - 28405599
SN - 2373-8731
VL - 3
SP - e143
JO - Transplantation direct
JF - Transplantation direct
IS - 4
ER -