Szymanska Sylwia, Markiewicz-Kijewska Malgorzata, Pyzlak Michal, Karkucinska-Wienckowska Agnieszka, Ciopinski Mateusz, Czubkowski Piotr, Kaliciński Piotr
Department of Pathology, The Children's Memorial Health Institute, 04-736 Warsaw, Poland.
Department of Pediatric Surgery and Organ's Transplantation, The Children's Memorial Health Institute, 04-736 Warsaw, Poland.
J Clin Med. 2023 Jun 26;12(13):4269. doi: 10.3390/jcm12134269.
Preclinical models have demonstrated that PD-1 and its ligand programmed death ligand1 (PD-L1) play significant roles in both graft induction and the maintenance of immune tolerance. It has also been suggested that PD-L1 tissue expression may predict graft rejection; however, the available data are sparse and inconclusive. Some studies were conducted on patients with cancer; most of them do not concern the liver, especially within the context of the use of immunohistochemical tests. Therefore, the aim of our study was to assess the relationship between tissue expression of PD-L1 in a unique material, i.e., in the liver biopsies of pediatric patients after transplantation with the presence of acute cellular rejection (ACR).
This retrospective study enrolled 55 biopsies from 55 patients who underwent protocol liver biopsies. The control group consisted of 19 biopsies from 13 patients diagnosed with acute cellular rejection (rejection activity index/RAI/ from 2 to 8). An immunohistochemical (IHC) staining for PD-L1 was performed in all of the liver specimens; its expression was analyzed in different regions of liver tissue (in inflammatory infiltrates and within the endothelium and hepatocytes). The following changes were re-evaluated in each specimen: features of any kind of rejection (acute cellular, antibody-mediated, chronic); the presence and severity of fibrosis (Ishak scale); and the presence of cholestasis and steatosis. Clinical parameters were also evaluated, including tests of liver function (AST, ALT, GGT, bilirubin).
The age of patients in the study group ranged from 2.37 to 18.9 years (median 13.87 years), with the time after transplantation being 1-17 years (median 8.36 years). The age of patients in the control group ranged from 1.48 to 17.51 years (median 7.93 years), with their biopsies being taken 0.62-14.39 years (median 1.33 years) after transplantation. We found a statistically significant relationship between PD-L1 expression on inflammatory infiltrates and ACR; however, there was no statistically significant relationship between PD-L1 endothelial expression and ACR. PD-L1 was not positive in the hepatocytes regardless of if it was the study or control group that was under observation.
PD-L1 appears to be a promising marker to predict graft rejection.
临床前模型已证明，程序性死亡受体1（PD-1）及其配体程序性死亡配体1（PD-L1）在移植诱导和免疫耐受维持中均发挥重要作用。也有研究表明，PD-L1的组织表达可能预测移植排斥反应；然而，现有数据稀少且尚无定论。一些研究是针对癌症患者开展的；其中大多数与肝脏无关，尤其是在使用免疫组织化学检测的情况下。因此，我们研究的目的是评估一种独特材料，即小儿移植患者肝活检组织中PD-L1的组织表达与急性细胞排斥反应（ACR）之间的关系。
本回顾性研究纳入了55例接受常规肝活检患者的55份活检样本。对照组包括13例诊断为急性细胞排斥反应（排斥活动指数/RAI/为2至8）患者的19份活检样本。对所有肝脏标本进行PD-L1的免疫组织化学（IHC）染色；分析其在肝组织不同区域（炎症浸润、内皮细胞和肝细胞内）的表达情况。对每个标本重新评估以下变化：任何类型排斥反应（急性细胞性、抗体介导性、慢性）的特征；纤维化的存在及严重程度（伊沙克分级）；胆汁淤积和脂肪变性的存在情况。还评估了临床参数，包括肝功能检查（谷草转氨酶、谷丙转氨酶、γ-谷氨酰转肽酶、胆红素）。
研究组患者年龄为2.37至18.9岁（中位数13.87岁），移植后时间为1至17年（中位数8.36年）。对照组患者年龄为1.48至17.51岁（中位数7.93岁），活检在移植后0.62至14.39年（中位数1.33年）进行。我们发现炎症浸润上PD-L1表达与ACR之间存在统计学显著关系；然而，PD-L1在内皮细胞上的表达与ACR之间无统计学显著关系。无论观察的是研究组还是对照组，肝细胞中的PD-L1均为阴性。
PD-L1似乎是预测移植排斥反应的一个有前景的标志物。
