Department of Nephrology Laboratory of Experimental Nephrology, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
Am J Transplant. 2011 Oct;11(10):2162-72. doi: 10.1111/j.1600-6143.2011.03633.x. Epub 2011 Jul 12.
Presence of subclinical rejection (SCR) with IF/TA in protocol biopsies of renal allografts has been shown to be an independent predictor factor of graft loss. Also, intragraft Foxp3+ T(reg) cells in patients with SCR has been suggested to differentiate harmful from potentially protective infiltrates. Nonetheless, whether presence of Foxp3 T(reg) cells in patients with SCR and IF/TA may potentially protect from a deleterious graft outcome has not yet been evaluated. This is a case-control study in which 37 patients with the diagnosis of SCR and 68 control patients with no cellular infiltrates at 6-month protocol biopsies matched for age and time of transplantation were evaluated. We first confirmed that numbers of intragraft Foxp3-expressing T cells in patients with SCR positively correlates with Foxp3 demethylation at the T(reg) -specific demethylation region. Patients with SCR without Foxp3+ T(reg) cells within graft infiltrates showed significantly worse 5-year graft function evolution than patients with SCR and Foxp3+ T(reg) cells and those without SCR. When presence of SCR and IF/TA were assessed together, presence of Foxp3+ T(reg) could discriminate a subgroup of patients showing the same graft outcome as patients with a normal biopsy. Thus, presence of Foxp3+ T(reg) cells in patients with SCR even with IF/TA is associated with a favorable long-term allograft outcome.
移植肾活检中存在亚临床排斥反应(SCR)伴免疫荧光/组织化学染色阳性(IF/TA)已被证实是移植物丢失的独立预测因素。此外,SCR 患者移植组织内 Foxp3+T 调节细胞(Treg)已被认为可区分有害和潜在保护性浸润。然而,SCR 伴 IF/TA 患者的 Foxp3+Treg 细胞是否可能对有害移植物结局有保护作用尚未得到评估。本研究为病例对照研究,纳入 37 例 SCR 患者和 68 例年龄和移植时间匹配的 6 个月时移植肾活检未见细胞浸润的对照组患者。首先,我们证实 SCR 患者移植组织内 Foxp3 表达 T 细胞数量与 Treg 特异性去甲基化区 Foxp3 去甲基化呈正相关。与 SCR 伴 Foxp3+Treg 细胞和无 SCR 的患者相比,SCR 患者移植组织内无 Foxp3+Treg 细胞的患者 5 年移植物功能演变明显较差。当同时评估 SCR 和 IF/TA 时,Foxp3+Treg 的存在可区分一组与活检正常患者具有相同移植物结局的患者。因此,SCR 患者即使存在 IF/TA,Foxp3+Treg 细胞的存在也与长期移植物预后良好相关。