Early Cytomegalovirus Reactivation in Renal Recipients Is Associated with High Levels of B Cell Maturation Antigen Transcript Expression Prior to Transplantation

Abstract

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.

Bifidobacterium longum Subsp. infantis Promotes IgA Level of Growing Mice in a Strain-Specific and Intestinal Niche-Dependent Manner

“…BCMA is a receptor for BAFF, which plays an important role in the maturation and function of B cells [ 35 ]. When BAFF binds to BCMA, it can trigger a series of downstream signal transduction pathways, thereby promoting the survival and differentiation of B cells [ 35 ]. APRIL can bind to both BCMA and TACI to activate B cells, promoting IgA synthesis and secretion [ 36 ].…”

Incidence, risk factors, management strategies and outcomes of antibody-mediated rejection in pediatric kidney transplant recipients – a multicenter analysis of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN)

“…These molecules of the BAFF system have also been suggested as biomarkers for the development of alloantibodies and graft dysfunction. Recently, early CMV reactivation in kidney transplant recipients has been shown to be associated with high levels of BCMA transcript expression prior to transplantation [20]. However, the exact mechanisms by which CMV may contribute to the development of ABMR remain incompletely understood and require further study.…”

MicroRNAs as Potential Graft Rejection or Tolerance Biomarkers and Their Dilemma in Clinical Routines Behaving like Devilish, Angelic, or Frightening Elements

“…It is known and inferred that different changes in miRNA expression could modify or modulate kidney transplantation's short-and long-term evolution. The vast majority of studies on kidney allograft transplantation that direct or analyze the role of miRNAs or mRNA detection and expression have been conducted with blood samples (isolating cells as peripheral blood leukocytes or separating plasma or serum) or urine samples, and a small percentage of studies have analyzed the expression of intra-graft miRNAs comparing their eventual correlation with the levels of the rest of the mRNA [5,6,8,63]. RNA quantification indirectly measures the gene expression levels in a person's blood, cells, fluids, or tissues.…”

“…Several articles from recent years emphasize the function of miRNA expression in solid organ transplantation and imply that it has a role in the acceptance or rejection of allografts [21,63].…”

“…Numerous B lymphocyte subpopulations, including germline naive B lymphocytes, have had their expression of miRNAs examined, demonstrating that these molecules may be crucial for effector activities and regulatory networks governing cell growth [63,71]. In this manner, different miRNAs have been implicated in B cell function and antibody production.…”