van den Hoogen Martijn W F, Steenbergen Eric J, Baas Marije C, Florquin Sandrine, Hilbrands Luuk B
Renal Transplant Unit, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
Transplant Direct. 2017 Mar 10;3(4):e143. doi: 10.1097/TXD.0000000000000659. eCollection 2017 Apr.
The pathophysiological role of intragraft B cells during renal allograft rejection is unclear.
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) 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.
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%; = 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; < 0.0001) and plasma cells (0.10; range, 0.00-1.90 vs 0.40; range, 0.00-7.50; = 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).
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.
肾移植排斥反应期间移植物内B细胞的病理生理作用尚不清楚。
我们研究了53例参与一项临床试验患者急性排斥反应期间的B细胞浸润情况，该试验将成年肾移植患者随机分为术中单次给予利妥昔单抗（375mg/m）或安慰剂作为诱导治疗。两名独立病理学家根据Banff分类法以盲法对所有活检标本进行评分，并使用CD79a和CD138作为标志物对B细胞和浆细胞的存在情况进行评分。
大多数急性排斥反应是由T细胞介导的。利妥昔单抗治疗的患者中具有抗体介导成分的急性排斥反应比例往往低于安慰剂治疗的患者（4/23，17.4% 对比11/30，36.7%；P = 0.14）。利妥昔单抗治疗患者的活检标本中B细胞（0.00；范围，0.00 - 0.50对比1.70；范围，0.60 - 3.30；P < 0.0001）和浆细胞（0.10；范围，0.00 - 1.90对比0.40；范围，0.00 - 7.50；P = 0.006）的评分显著更低。在急性排斥反应期间，利妥昔单抗诱导治疗后未观察到移植物内B细胞簇。然而，急性排斥反应期间移植物内B细胞的耗竭并不影响类固醇抵抗、蛋白尿、2年随访时的移植物功能，或在中位随访4.1年（范围，2.0 - 6.2年）时的患者和移植物存活情况。
这些数据不支持急性同种异体移植排斥反应期间存在的移植物内B细胞对肾移植后最初几年临床病程产生有害影响。
