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探讨 BAFF 及其受体在慢性抗体介导的排斥反应的肾移植受者中的作用。

Investigating the Role of BAFF and Its Receptors in Renal Transplant Recipients with Chronic Antibody-Mediated Rejection.

机构信息

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

J Immunol Res. 2021 Mar 6;2021:6654992. doi: 10.1155/2021/6654992. eCollection 2021.

Abstract

BACKGROUND

Kidney transplantation is the best treatment option for end stage renal disease (ESRD), but graft rejection is still a big obstacle that occurs in spite of immunosuppressive therapy. B cells are considered as the major reason for renal graft rejection because of antibody production. Due to their roles in B cell function, we intended to evaluate the B cell activating factor (BAFF) and its receptors including BAFF receptor (BAFF-R), B cell maturation antigen (BCMA), and transmembrane activator and cyclophilin ligand interactor (TACI) in renal transplant patients.

METHOD

The study included 40 kidney allograft patients with cAMR, 40 stable kidney allograft patients, and 8 healthy volunteers with normal kidney function. The percentage and absolute number of CD19 B cells were analyzed by flow cytometry, the serum level of BAFF was analyzed by ELISA, and mRNA expressions of BAFF and BAFF receptors (BAFF-R, BCMA, and TACI) were measured using quantitative real-time PCR.

RESULTS

The percentage and the absolute number of B cells decreased significantly in stable and cAMR patients compared to healthy individuals. The serum level and gene expression of BAFF, as well as the mRNA level of BCMA, were increased significantly in both cAMR and stable patients compared to healthy volunteers. There was an overexpression of TACI mRNA in cAMR patients compared to stable patients.

CONCLUSIONS

Both soluble protein and mRNA transcript of BAFF increased in transplant recipients. However, BAFF neither at the serum level nor at the mRNA transcript level cannot be a good biomarker for the prediction of cAMR. In addition, expression of TACI, compared to other receptors of BAFF, confers a potential to be used in distinguishing cAMR and stable kidney transplant patients.

摘要

背景

肾移植是终末期肾病(ESRD)的最佳治疗选择,但移植物排斥仍然是一个很大的障碍,尽管进行了免疫抑制治疗。B 细胞被认为是导致肾移植排斥的主要原因,因为它们可以产生抗体。由于它们在 B 细胞功能中的作用,我们旨在评估 B 细胞激活因子(BAFF)及其受体,包括 BAFF 受体(BAFF-R)、B 细胞成熟抗原(BCMA)和跨膜激活剂和钙环素配体相互作用蛋白(TACI)在肾移植患者中的作用。

方法

该研究包括 40 例伴有 cAMR 的肾移植患者、40 例稳定的肾移植患者和 8 例肾功能正常的健康志愿者。通过流式细胞术分析 CD19 B 细胞的百分比和绝对数,通过 ELISA 分析 BAFF 血清水平,通过定量实时 PCR 测量 BAFF 和 BAFF 受体(BAFF-R、BCMA 和 TACI)的 mRNA 表达。

结果

与健康个体相比,稳定和 cAMR 患者的 B 细胞百分比和绝对数显著下降。与健康志愿者相比,cAMR 和稳定患者的 BAFF 血清水平和基因表达以及 BCMA 的 mRNA 水平均显著升高。与稳定患者相比,cAMR 患者的 TACI mRNA 表达过度。

结论

移植受者中 BAFF 的可溶性蛋白和 mRNA 转录物均增加。然而,BAFF 无论是在血清水平还是在 mRNA 转录水平都不能作为 cAMR 预测的良好生物标志物。此外,与 BAFF 的其他受体相比,TACI 的表达具有用于区分 cAMR 和稳定肾移植患者的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfe4/7959970/42572979d1da/JIR2021-6654992.001.jpg

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