Immunology Service, Hospital Clinico Universitario Virgen de la Arrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain.
Nephrology Services, Hospital Clinico Universitario Virgen de la Arrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain.
Int J Mol Sci. 2023 Jun 22;24(13):10491. doi: 10.3390/ijms241310491.
Cytomegalovirus (CMV) infection is the most frequent infection episode in kidney transplant (KT) recipients. Reactivation usually occurs in the first three months after transplantation and is associated with higher cellular and/or antibody-mediated rejection rates and poorer graft performance. CMV induces the expression of BAFF (B-cell-activating factor, a cytokine involved in the homeostasis of B cells), which communicates signals for survival and growth to B cells and virus-specific plasma cells via the R-BAFF (BAFF receptor), TACI (the calcium modulator, the cyclophilin ligand interactor), and BCMA (B cell maturation antigen) receptors. These molecules of the BAFF system have also been suggested as biomarkers for the development of alloantibodies and graft dysfunction. This prospective study included 30 CMV-IgG seropositive KT recipients. The expression levels of the genes BAFF-R, transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA) in peripheral blood leukocytes (PBL) pre-KT were determined using qPCR. qPCR was also used to monitor CMV reactivation in the first three months following KT. The remainder of the KT recipients were classified as CMV- reactivation, and those with more than 500 copies/mL in at least one sample were classified as CMV+ reactivation. There were no discernible variations in the BAFF-R and TACI transcript expression levels. In the CMV+ group, we examined the relationship between the transcript levels and peak viremia. Peak viremia levels and BCMA transcript levels showed a strong correlation. BAFF-R and TACI expressions showed no measurable differences. In patients with early CMV reactivation, high BCMA receptor expression was associated with increased plasmablast, lymphocyte B cell class-switched levels (LBCS), and viral load. Our findings demonstrate that pre-KT BCMA transcript levels increased in KT recipients with early CMV reactivation. These transcript levels positively correlate with peak viremia and weakly with plasmablast and LBCS levels in PBLs.
巨细胞病毒 (CMV) 感染是肾移植 (KT) 受者最常见的感染事件。病毒再激活通常发生在移植后三个月内，与更高的细胞和/或抗体介导的排斥反应率以及更差的移植物功能相关。CMV 诱导 BAFF（B 细胞激活因子，一种参与 B 细胞稳态的细胞因子）的表达，通过 BAFF 受体 (R-BAFF)、跨膜激活剂和钙调磷酸酶配体相互作用蛋白 (TACI)、B 细胞成熟抗原 (BCMA) 受体向 B 细胞和病毒特异性浆细胞传递存活和生长信号。BAFF 系统的这些分子也被认为是同种抗体和移植物功能障碍发展的生物标志物。这项前瞻性研究纳入了 30 名 CMV-IgG 阳性的 KT 受者。使用 qPCR 测定外周血白细胞 (PBL) 中 BAFF-R、跨膜激活剂和钙调磷酸酶配体相互作用蛋白 (TACI) 和 B 细胞成熟抗原 (BCMA) 的基因表达水平。qPCR 还用于监测 KT 后三个月内 CMV 的再激活。其余的 KT 受者被分类为 CMV 再激活，至少有一个样本中病毒载量超过 500 拷贝/mL 的受者被分类为 CMV+再激活。BAFF-R 和 TACI 转录表达水平没有明显变化。在 CMV+组中，我们研究了转录水平与峰值病毒血症之间的关系。峰值病毒血症水平与 BCMA 转录水平呈强相关性。BAFF-R 和 TACI 的表达没有明显差异。在早期 CMV 再激活的患者中，高 BCMA 受体表达与浆母细胞、淋巴细胞 B 细胞类别转换水平 (LBCS) 和病毒载量增加相关。我们的研究结果表明，在早期 CMV 再激活的 KT 受者中，BCMA 转录水平在移植前升高。这些转录水平与峰值病毒血症呈正相关，与 PBL 中的浆母细胞和 LBCS 水平呈弱相关。
