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

• Published in: International journal of molecular sciences 2023-06, Vol.24 (13), p.10491
• Main Authors: Alfaro, Rafael, Rodríguez-Aguilar, Luis, Llorente, Santiago, Jimenez-Coll, Victor, Martínez-Banaclocha, Helios, Galián, José Antonio, Botella, Carmen, Moya-Quiles, María Rosa, Muro-Perez, Manuel, Minguela, Alfredo, Legaz, Isabel, Muro, Manuel
• Format: Article
• Language: English
• Subjects: acute rejection; Alloantibodies; Allografts; Antibodies; Antigens; B cells; B-Cell Activating Factor - genetics; B-Cell Maturation Antigen - genetics; B-Cell Maturation Antigen - metabolism; BAFF gene expression; BCMA; Biomarkers; Biopsy; BLyS protein; Cells; CMV; Cytokines; Cytomegalovirus; Cytomegalovirus infections; Gene expression; Genetic research; Graft rejection; Health aspects; Homeostasis; Humans; Immunity; Immunoglobulin G; Infection; Infections; kidney transplant; Kidney transplants; Kidneys; Leukocytes; Ligands; Lymphocytes; Lymphocytes B; Maturation; Medical equipment and supplies industry; Medical research; Medical test kit industry; Peripheral blood; Plasma; Plasma cells; plasmablast; Prospective Studies; Rejection rate; Transmembrane Activator and CAML Interactor Protein - genetics; Transplantation; Viremia; Virus diseases
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.