Grimm P C, Sinai-Trieman L, Sekiya N M, Robertson L S, Robinson B J, Fine R N, Ettenger R B
Pediatric Histocompatibility Laboratory, UCLA School of Medicine Los Angeles.
Kidney Int. 1990 Jul;38(1):12-8. doi: 10.1038/ki.1990.161.
Highly presensitized patients wait longer for a renal allograft than unsensitized patients and have a poorer allograft survival rate. Repeated blood transfusions have been implicated in the induction and maintenance of sensitization. To determine the effect of recombinant human erythropoietin (rHuEPO) therapy on five transfusion dependent, highly sensitized adolescents on dialysis, we serially measured percentage panel reactive antibody (%PRA) levels, titers of identifiable discrete anti-HLA Class I antibody specificities, and non-specific indices of cellular immunity before and following initiation of rHuEPO therapy. Although four of the five patients had previously rejected at least one renal allograft, the removal of chronic antigenic stimulation from blood transfusions led to a marked reduction in anti-HLA antibody titers to recognizable private and public specificities (P less than 0.001) and a reduction of mean %PRA from 80% to 56% (P less than 0.05). Each patient demonstrated a reduction of two or more dilutions to at least two anti-HLA antibody specificities. A control group of five patients matched for age, transfusion dependence and sensitization status demonstrated no change during a comparable time interval. PHA responsiveness decreased significantly in the rHuEPO group whereas autologous and allogenic mixed lymphocyte response, spontaneous blastogenesis and T-cell subsets did not. These data indicate that in highly sensitized dialysis patients rHuEPO may lead to decreased sensitization, shorter waiting time on dialysis and possibly improved allograft survival rates.
高度致敏的患者等待肾移植的时间比未致敏的患者更长，且移植肾的存活率更低。反复输血被认为与致敏的诱导和维持有关。为了确定重组人促红细胞生成素（rHuEPO）治疗对五名依赖输血、高度致敏的透析青少年的影响，我们在开始rHuEPO治疗之前和之后，连续测量了群体反应性抗体百分比（%PRA）水平、可识别的离散抗HLA I类抗体特异性滴度以及细胞免疫的非特异性指标。尽管五名患者中有四名此前至少排斥过一次肾移植，但停止输血带来的慢性抗原刺激消除，导致抗HLA抗体滴度显著降低至可识别的个体和公共特异性水平（P<0.001），平均%PRA从80%降至56%（P<0.05）。每名患者针对至少两种抗HLA抗体特异性的稀释度降低了两个或更多。一个由五名年龄、输血依赖性和致敏状态相匹配的患者组成的对照组在相当的时间间隔内未出现变化。rHuEPO组的PHA反应性显著降低，而自体和同种异体混合淋巴细胞反应、自发母细胞形成和T细胞亚群则没有变化。这些数据表明，对于高度致敏的透析患者，rHuEPO可能会降低致敏程度，缩短透析等待时间，并可能提高移植肾的存活率。
