title: Kidney transplant recipients treated with belatacept exhibit increased naïve and transitional B cells.
abstract: 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(+) CD24(hi) CD38(hi) and CD19(+) IgD(hi) CD38(hi) CD27(-) , 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.
authors.affiliation: Nephrology and Transplantation Department, CHU Henri Mondor, APHP, Créteil, France; Unité Inserm U955, équipe 21 and CIC Biothérapies 504, CHU Henri Mondor, APHP, Paris XII University, Créteil, France.
authors.forename: C
authors.initials: C
authors.lastname: Leibler
authors.forename: M
authors.initials: M
authors.lastname: Matignon
authors.forename: C
authors.initials: C
authors.lastname: Pilon
authors.forename: F
authors.initials: F
authors.lastname: Montespan
authors.forename: J
authors.initials: J
authors.lastname: Bigot
authors.forename: P
authors.initials: P
authors.lastname: Lang
authors.forename: E D
authors.initials: ED
authors.lastname: Carosella
authors.forename: J
authors.initials: J
authors.lastname: Cohen
authors.forename: N
authors.initials: N
authors.lastname: Rouas-Freiss
authors.forename: P
authors.initials: P
authors.lastname: Grimbert
authors.forename: C
authors.initials: C
authors.lastname: Menier
mesh_terms: D000069594:Abatacept; D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism; D053265:B-Cell Activation Factor Receptor / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D066027:Transplant Recipients
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D000069594:Abatacept
keywords: BAFF; BAFF-R; CTLA-4-Ig; belatacept; kidney transplantation; transitional B cells