Department of Nephrology and Transplantation Medicine, Wrocław Medical University, Wrocław, Poland.
Lower Silesian Oncology Center, Wrocław, Poland.
Ann Transplant. 2023 Nov 28;28:e941266. doi: 10.12659/AOT.941266.
BACKGROUND Toll-like receptor 3 expression is detected both on the cell membrane and in endosomes of peripheral blood mononuclear cells (PBMC). Our goal in this study was to determine to what extent a single, baseline measurement of non-stimulated PBMC TLR3-mRNA can be related to baseline GFR (b-GFR) and post-follow-up-GFR (F-up-GFR) of a kidney transplant (KT) and baseline immunosuppression. MATERIAL AND METHODS In non-stimulated PBMC we investigated averaged mRNA expression of Toll-like receptor 3. A total of 133 patients were enrolled; the median of months after KT surgery was 11.4, with median F-up at 21.3 months. A favorable course (FCF) was determined if F-up-eGFR improved. An unfavorable course (UCF) was determined if F-up-eGFR was lower at the end of the observation. RESULTS The highest TLR3-mRNA expression was at b-GFR grade 3b; it was moderately higher at b-GFR grade 3a, and marginally higher at b-GFR grades 1+2. Most of the FCF group had b-GFR grade 3b, less frequent obesity, more effective immunosuppression, and much higher TLR3-mRNA (59% of cases were in the high-TLR3 area). Both delayed graft function (DGF) and TLR3-mRNA range below the median for the entire KT cohort (low-TLR3 area) had a negative association with b-GFR. The UCF group had more frequent DGFs and obesity, less effective immunosuppression, and lower TLR3-mRNA. CONCLUSIONS In patients with GFR grade 3, high levels of TLR3-mRNA are associated with improved graft efficacy. In patients with impaired graft function, low TLR3- mRNA expression reduces the likelihood of improved renal graft function.
Toll 样受体 3 表达可在外周血单个核细胞(PBMC)的细胞膜和内体中检测到。我们在这项研究中的目标是确定单个基线非刺激 PBMC TLR3-mRNA 测量与肾移植(KT)的基线肾小球滤过率(b-GFR)和随访后肾小球滤过率(F-up-GFR)以及基线免疫抑制的关系程度。
在非刺激的 PBMC 中,我们研究了 Toll 样受体 3 的平均 mRNA 表达。共纳入 133 例患者;KT 手术后中位数为 11.4 个月,中位数随访时间为 21.3 个月。如果随访时 eGFR 改善,则确定为良好病程(FCF)。如果在观察结束时随访时 eGFR 较低,则确定为不良病程(UCF)。
TLR3-mRNA 表达最高的是 b-GFR 分级 3b;b-GFR 分级 3a 时略高,b-GFR 分级 1+2 时略高。大多数 FCF 组的 b-GFR 分级为 3b,肥胖症较少,免疫抑制作用更有效,TLR3-mRNA 水平更高(59%的病例处于高 TLR3 区)。延迟移植物功能(DGF)和 TLR3-mRNA 范围均低于整个 KT 队列的中位数(低 TLR3 区)与 b-GFR 呈负相关。UCF 组的 DGF 和肥胖症更为常见,免疫抑制作用更差,TLR3-mRNA 水平更低。
在 GFR 分级为 3 的患者中,高水平的 TLR3-mRNA 与移植物疗效改善相关。在移植物功能受损的患者中,低 TLR3-mRNA 表达降低了改善肾移植功能的可能性。