Early Cytomegalovirus Reactivation in Renal Recipients Is Associated with High Levels of B Cell Maturation Antigen Transcript Expression Prior to Transplantation.
Rafael Alfaro, Luis Rodríguez-Aguilar, Santiago Llorente, Victor Jimenez-Coll, Helios Martínez-Banaclocha, José Antonio Galián, Carmen Botella, María Rosa Moya-Quiles, Manuel Muro-Perez, Alfredo Minguela, Isabel Legaz, Manuel Muro
Author Information
Rafael Alfaro: Immunology Service, Hospital Clinico Universitario Virgen de la Arrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain.
Luis Rodríguez-Aguilar: Immunology Service, Hospital Clinico Universitario Virgen de la Arrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain.
Santiago Llorente: Nephrology Services, Hospital Clinico Universitario Virgen de la Arrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain. ORCID
Victor Jimenez-Coll: Immunology Service, Hospital Clinico Universitario Virgen de la Arrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain.
Helios Martínez-Banaclocha: Immunology Service, Hospital Clinico Universitario Virgen de la Arrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain.
José Antonio Galián: Immunology Service, Hospital Clinico Universitario Virgen de la Arrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain.
Carmen Botella: Immunology Service, Hospital Clinico Universitario Virgen de la Arrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain.
María Rosa Moya-Quiles: Immunology Service, Hospital Clinico Universitario Virgen de la Arrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain. ORCID
Manuel Muro-Perez: Immunology Service, Hospital Clinico Universitario Virgen de la Arrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain.
Alfredo Minguela: Immunology Service, Hospital Clinico Universitario Virgen de la Arrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain. ORCID
Isabel Legaz: Department of Legal and Forensic Medicine, Biomedical Research Institute of Murcia (IMIB), Regional Campus of International Excellence "Campus Mare Nostrum", Faculty of Medicine, University of Murcia, 30100 Murcia, Spain. ORCID
Manuel Muro: Immunology Service, Hospital Clinico Universitario Virgen de la Arrixaca (HCUVA), Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain. ORCID
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.
