Kidney Transplant Recipients Treated With Belatacept Exhibit Increased Naïve and Transitional B Cells

• Published in: American journal of transplantation Vol. 14; no. 5; pp. 1173 - 1182
• Main Authors: Leibler, C., Matignon, M., Pilon, C., Montespan, F., Bigot, J., Lang, P., Carosella, E. D., Cohen, J., Rouas‐Freiss, N., Grimbert, P., Menier, C.
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley 01.05.2014; Elsevier Limited
• Subjects: Abatacept; B-Cell Activating Factor - genetics; B-Cell Activating Factor - metabolism; B-Cell Activation Factor Receptor - genetics; B-Cell Activation Factor Receptor - metabolism; BAFF; BAFF‐R; belatacept; Biological and medical sciences; Cells, Cultured; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Cohort Studies; CTLA‐4‐Ig; Female; Flow Cytometry; Follow-Up Studies; Graft Rejection - drug therapy; Graft Rejection - immunology; Graft Rejection - metabolism; Humans; Immunoconjugates - therapeutic use; Immunosuppressive Agents - therapeutic use; Kidney Failure, Chronic - surgery; Kidney Transplantation; Male; Medical sciences; Middle Aged; Precursor Cells, B-Lymphoid - cytology; Precursor Cells, B-Lymphoid - metabolism; Prognosis; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system; transitional B cells; Transplant Recipients; BAFF; Immunoglobulins; transitional B cells; Cytokine; Naive cell; Belatacept; B-Lymphocyte; Homotransplantation; Kidney; Cytotoxic T lymphocyte antigen 4; B cell activating factor receptor; Immunomodulator; BAFF-R; Treatment; Urinary system; Tumor necrosis factor; Surgery; B cell activating factor; Graft; β Cell; Immunosuppressive agent; Fusion protein; CTLA-4-Ig; Kidney transplantation; belatacept; kidney transplantation
• ISSN: 1600-6135; 1600-6143; 1600-6143
• DOI: 10.1111/ajt.12721

Phase III clinical studies have shown that kidney transplant (KT) recipients treated with the costimulation blocker belatacept exhibited a better renal allograft function and lower donor‐specific anti‐HLA immunization when compared to recipients treated with calcineurin inhibitors (CNI). We analyzed B cell phenotype in KT recipients treated with belatacept and stable renal function (N = 13). Results were compared to those observed in stable patients treated with CNI (N = 12), or with chronic antibody‐mediated rejection (N = 5). Both transcriptional profile and phenotypic characterization of peripheral B cells were performed by real‐time polymerase chain reaction and flow cytometry, respectively. In belatacept group, the frequency and absolute number of transitional B cells as defined by both phenotypes: CD19+CD24hiCD38hi and CD19+IgDhiCD38hiCD27−, as well as naïve B cells were significantly higher compared with CNI group. B cell activating factor (BAFF) and BAFF receptor mRNA levels were significantly lower in belatacept group than in CNI group. These results show for the first time that belatacept influences B cell compartment by favoring the occurrence of transitional B cells with potential regulatory properties, as described in operational tolerant patients. This role may explain the lower alloimmunization rate observed in belatacept‐treated patients. The authors report a B cell phenotype analysis in kidney transplant recipients who have stable renal function on belatacept maintenance immunosuppression, and show that belatacept influences the B cell compartment by favoring the occurrence of transitional B cells as described in operationally tolerant patients. (Also see article by Kirk et al on page 1142.)