Department of Kidney Transplantation, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China.
Department of Kidney Transplantation and Kidney Transplantation Research Laboratory, Tianjin First Central Hospital, Tianjin, China.
Front Immunol. 2021 Apr 9;12:661911. doi: 10.3389/fimmu.2021.661911. eCollection 2021.
Chronic active antibody-mediated rejection (CAAMR) is an intermediate process that occurs during the development of chronic antibody-mediated rejection (CAMR), which is a key problem associated with the long-term kidney grafts survival. This study investigated the role played by PC3-secreted microprotein (PSMP) in the progression of CAAMR and CAMR. We showed that CAAMR and CAMR patients' allografts dysfunction with declined survival rate, which suggested that earlier diagnosis and treatment of CAAMR might be important to prevent irreversible chronic injury of CAMR progression. We found PSMP was an important factor in the development of chronic antibody-mediated rejection. The PSMP expression increased significantly in CAAMR biopsy samples but not in CAMR and control patients, which distinguished CAAMR patients from CAMR and non-rejection patients. Moreover, our results showed that infiltration of CD68 macrophages in CAAMR increased, and the correlation between CD68 macrophages and PSMP expression in CAAMR patients was significant. Additionally, our data also revealed that intimal arteritis (v-lesion) accompanied by increased macrophage infiltration might have contributed to more graft loss in CAAMR, and PSMP expression was significantly associated with the v-lesion score. These results indicated that PSMP played an important role in the recruitment of macrophages and promote intimal arteritis inducing allograft lost in CAAMR progression. In future study PSMP could be a potential histopathological diagnostic biomarker and treatment target for CAAMR in kidney transplantation.
慢性活动性抗体介导的排斥反应(CAAMR)是慢性抗体介导的排斥反应(CAMR)发展过程中的一个中间过程,是与长期肾脏移植物存活相关的一个关键问题。本研究探讨了 PC3 分泌的微蛋白(PSMP)在 CAAMR 和 CAMR 进展中的作用。我们发现 CAAMR 和 CAMR 患者的同种异体移植物功能障碍,存活率下降,这表明早期诊断和治疗 CAAMR 可能对防止 CAMR 进展的不可逆慢性损伤很重要。我们发现 PSMP 是慢性抗体介导的排斥反应发展的一个重要因素。CAAMR 活检样本中 PSMP 的表达显著增加,但在 CAMR 和对照组患者中没有增加,这将 CAAMR 患者与 CAMR 和非排斥患者区分开来。此外,我们的结果表明,CAAMR 中 CD68 巨噬细胞浸润增加,CAAMR 患者中 CD68 巨噬细胞与 PSMP 表达之间存在显著相关性。此外,我们的数据还表明,伴随巨噬细胞浸润增加的内膜性动脉炎(v 病变)可能导致 CAAMR 中更多的移植物丢失,PSMP 表达与 v 病变评分显著相关。这些结果表明 PSMP 在募集巨噬细胞和促进内膜性动脉炎诱导 CAAMR 进展中的同种异体移植物丢失方面发挥了重要作用。在未来的研究中,PSMP 可能成为肾移植中 CAAMR 的潜在组织病理学诊断生物标志物和治疗靶点。