Does Borderline Kidney Allograft Rejection Always Require Treatment?
Does Borderline Kidney Allograft Rejection Always Require Treatment?
复制标题
边缘性肾同种异体移植排斥是否总是需要治疗？
作者：
Dorottya Németh;J. Ovens;G. Opelz;C. Sommerer;B. Döhler;L. E. Becker;M. Gross;R. Waldherr;M. Mieth;M. Sadeghi;Jan Schmidt;R. Langer;M. Zeier;C. Süsal
背景边缘性排斥反应（Bordline rejection，Bord-R）是肾移植中常见的排斥反应，越来越多的证据表明调节性T淋巴细胞参与了其发病机制。目前的组织病理学实践并不区分移植物保护性和损伤性T淋巴细胞，Bord-R患者常规接受排斥治疗。我们分析了Treg相关叉头盒P3（Foxp 3）基因在Bord-R和更严重形式的急性排斥反应（ARE）中的表达。方法. Foxp 3转录测定520系列外周血样本从177个肾移植受者在移植后的第一个20天内获得。结果在Bord-R或无排斥反应的患者中观察到Foxp 3转录最高，而在ARE患者中最低。在移植后第5至7天，Bord-R患者的Foxp 3转录水平增加了156%，到移植后第14至16天增加到302%。相反，ARE患者的Foxp 3基因表达明显低于Bord-R、非排斥反应或急性肾小管坏死患者（在第11-13天分别为P=0.001、P<0.001和P=0.005）。急性肾小管坏死患者表现出中度高Foxp 3基因表达。结论.我们的数据表明，外周血中Treg活性增加是Bord-R的常见特征。这一发现质疑了所有组织病理学诊断为“Bord-R”的患者接受排斥治疗的适当性。
Background. Borderline rejection (Bord-R) is a frequent diagnosis in renal transplantation, and there is increasing evidence that regulatory T lymphocytes are involved in its pathogenesis. Current histopathologic practice does not differentiate between graft-protecting and -damaging T lymphocytes, and patients with Bord-R routinely receive rejection treatment. We analyzed Treg-associated forkhead box P3 (Foxp3) gene expression in Bord-R and more severe forms of acute rejection episodes (ARE). Methods. Foxp3 transcripts were measured in 520 serial peripheral blood samples from 177 kidney graft recipients obtained during the first 20 days posttransplantation. Results. The highest Foxp3 transcripts were observed in patients with Bord-R or without rejection and the lowest in patients with ARE. Patients with Bord-R on posttransplant days 5 to 7 showed an increased Foxp3 transcript level of 156%, which increased to 302% by posttransplant days 14 to 16. In contrast, patients with ARE demonstrated significantly lower Foxp3 gene expression than that observed in Bord-R, nonrejectors, or acute tubular necrosis patients (P=0.001, P<0.001, and P=0.005, respectively, on days 11–13). Acute tubular necrosis patients demonstrated intermediately high Foxp3 gene expression. Conclusions. Our data indicate that increased Treg activity in peripheral blood is a frequent feature of Bord-R. This finding questions the appropriateness of rejection treatment in all patients with the histopathologic diagnosis “Bord-R”.