Nakada Yasuyuki, Yamamoto Izumi, Horita Shigeru, Kobayashi Akimitsu, Mafune Aki, Katsumata Haruki, Yamakawa Takafumi, Katsuma Ai, Kawabe Mayuko, Tanno Yudo, Ohkido Ichiro, Tsuboi Nobuo, Yamamoto Hiroyasu, Okumi Masayoshi, Ishida Hideki, Yokoo Takashi, Tanabe Kazunari
Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Clin Transplant. 2016 Nov;30(11):1417-1424. doi: 10.1111/ctr.12833. Epub 2016 Sep 16.
The low sensitivity of C4d immunoreactivity in peritubular capillaries (PTCs) hinders its use in the diagnosis of chronic active antibody-mediated rejection (CAAMR). C4d-negative CAAMR was defined in the 2013 Banff classification, which included the expression of endothelial-associated transcripts (ENDATs). We previously showed that the ENDAT caveolin-1 (CAV-1) is a distinct feature of CAAMR. In this study, we investigated the prognostic value of CAV-1 immunoreactivity in PTCs in kidney transplant patients. Ninety-eight kidney transplant recipients were included in this study. The prognostic value of CAV-1 immunoreactivity in PTCs was evaluated by double immunostaining for CAV-1 and pathologische Anatomie Leiden endothelium (PAL-E, a PTC marker) in the PTCs of kidney allograft biopsy samples. The patients were divided into two groups: CAV-1/PAL-E<50% and CAV-1/PAL-E≥50%. Kaplan-Meier curves showed that CAV-1/PAL-E≥50% patients had a significantly worse prognosis than that of CAV-1/PAL-E<50% patients (log-rank; P<.001). C4d staining of PTCs was not associated with the development of graft failure (log-rank; P=.345), whereas in a multivariate Cox regression analysis, CAV-1 immunoreactivity in PTCs was independently associated with graft failure (hazard ratio: 11.1; P=.0324). CAV-1 immunoreactivity in PTCs may serve as a prognostic marker for kidney allograft survival.
肾小管周围毛细血管（PTCs）中C4d免疫反应性的低敏感性阻碍了其在慢性活动性抗体介导排斥反应（CAAMR）诊断中的应用。2013年班夫分类中定义了C4d阴性的CAAMR，其中包括内皮相关转录本（ENDATs）的表达。我们之前表明ENDAT小窝蛋白-1（CAV-1）是CAAMR的一个独特特征。在本研究中，我们调查了肾移植患者PTCs中CAV-1免疫反应性的预后价值。本研究纳入了98名肾移植受者。通过对同种异体肾活检样本的PTCs中CAV-1和病理解剖学莱顿内皮（PAL-E，一种PTC标志物）进行双重免疫染色，评估PTCs中CAV-1免疫反应性的预后价值。患者被分为两组：CAV-1/PAL-E<50%和CAV-1/PAL-E≥50%。Kaplan-Meier曲线显示，CAV-1/PAL-E≥50%的患者预后明显比CAV-1/PAL-E<50%的患者差（对数秩检验；P<.001）。PTCs的C4d染色与移植失败的发生无关（对数秩检验；P=.345），而在多变量Cox回归分析中，PTCs中CAV-1免疫反应性与移植失败独立相关（风险比：11.1；P=.0324）。PTCs中CAV-1免疫反应性可能作为同种异体肾存活的预后标志物。
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