Currently, Stanford University, Palo Alto, CA 94304, USA.
Transplantation. 2011 May 15;91(9):1010-8. doi: 10.1097/TP.0b013e318213df29.
Recently published pediatric trial of Rituximab for the treatment of CD20+ acute renal allograft rejection (AR) demonstrated transient depletion of circulating/intragraft B cells (Zarkhin et al., Am J Transplant 2008; 8: 2607). In this study, we have evaluated phenotypic definition of circulating B-cell subsets before and after standard of care and B-cell depletional AR therapies.
We assessed peripheral B cells by flow cytometry at the time of AR and after AR treatment in 35 pediatric renal transplant recipients: 17 patients with AR who received Rituximab (R-AR; n=11) or steroid pulsing (S-AR; n=6), 18 stable patients with stable graft function with (iSTA; n=10) or without interval infection (hSTA; n=8), and 3 healthy volunteers.
Infections increased memory (P=0.02) and CD19+/CD27⁻/IgD⁻ double negative (DN) B cells (P=0.02) and decreased naive B cells (P=0.01) in iSTA group compared to hSTA patients. Decrease in naive/memory B cells ratio at AR was observed compared with hSTA patients (P=0.01). One year after AR treatment, S-AR patients had persistently lower naive/memory B-cell ratio (P=0.01) and higher DN B cells (P=0.0001) than hSTA patients, whereas after R-AR treatment naive/memory B-cell ratio (P=0.6) and DN B cells (P=0.13) recovered to levels of hSTA patients. R-AR patients with sustained AR resolution (n=8) had trend toward better graft survival (P=0.06) and higher naive B cells (P=0.004) than R-AR relapsers (n=3).
Increase in circulating memory B cells was seen in pediatric patients at AR. B cells persist as memory after S-AR treatment, whereas Rituximab resulted in repopulation of mostly naive B cells. The heterogeneity in B-cells reconstitution after rejection therapies deserves further investigation as a possible means to follow the clinical and immunologic outcomes of graft rejection.
最近发表的一项关于利妥昔单抗治疗 CD20+急性肾移植排斥反应（AR）的儿科试验表明，循环/移植内 B 细胞（Zarkhin 等人，Am J Transplant 2008；8：2607）会短暂耗竭。在这项研究中，我们评估了标准治疗和 B 细胞耗竭性 AR 治疗前后循环 B 细胞亚群的表型定义。
我们通过流式细胞术在 35 名儿科肾移植受者 AR 时和 AR 治疗后评估外周 B 细胞：17 名接受利妥昔单抗（R-AR；n=11）或类固醇冲击（S-AR；n=6）的 AR 患者，18 名稳定的具有（iSTA；n=10）或不具有间隔感染（hSTA；n=8）的稳定移植物功能的患者，和 3 名健康志愿者。
与 hSTA 患者相比，iSTA 组的感染增加了记忆（P=0.02）和 CD19+/CD27⁻/IgD⁻双阴性（DN）B 细胞（P=0.02），并减少了幼稚 B 细胞（P=0.01）。与 hSTA 患者相比，AR 时幼稚/记忆 B 细胞比值降低（P=0.01）。与 hSTA 患者相比，S-AR 患者在 AR 后 1 年仍持续表现出较低的幼稚/记忆 B 细胞比值（P=0.01）和较高的 DN B 细胞（P=0.0001），而 R-AR 治疗后幼稚/记忆 B 细胞比值（P=0.6）和 DN B 细胞（P=0.13）恢复至 hSTA 患者的水平。持续缓解 AR 的 R-AR 患者（n=8）与 R-AR 复发患者（n=3）相比，其移植物存活率（P=0.06）更高，幼稚 B 细胞（P=0.004）更多。排斥治疗后 B 细胞重建的异质性值得进一步研究，因为这可能是监测移植物排斥的临床和免疫结果的一种手段。
