title: In kidney transplant patients, alemtuzumab but not basiliximab/low-dose rabbit anti-thymocyte globulin induces B cell depletion and regeneration, which associates with a high incidence of de novo donor-specific anti-HLA antibody development.
abstract: In this single-center matched-cohort study, we evaluated the phenotype of repopulating B cells and its correlation with donor-specific anti-HLA Ab development and long-term graft function in 16 renal transplant recipients and 32 age- and gender-matched controls induced with alemtuzumab or basiliximab (Bas)/low-dose rabbit anti-thymocyte globulin (rATG), respectively. Alemtuzumab, but not Bas/rATG, profoundly depleted peripheral B cells in the first 2 mo posttransplantation. Early posttransplant, naive B cells were significantly depleted, whereas Ag-experienced and memory B cells were partially spared. Transitional B cells transiently increased 2 mo posttransplant. At month 6 posttransplant, pregerminal center B cells emerged, a process promoted by increased BAFF serum levels. Thereafter, B cell counts increased progressively, mainly due to expansion of naive B cells. Conversely, Bas/rATG did not modify the B cell phenotype throughout the follow-up period. Alemtuzumab was associated with a higher incidence of de novo DSA compared with Bas/rATG. DSA development was predicted by changes in the B cell compartment and correlated with worse long-term graft function. Thus, alemtuzumab-induced B cell depletion/reconstitution may promote chronic humoral responses against the graft.
authors.affiliation: Centro Ricerche Trapianti "Chiara Cucchi de Alessandri e Gilberto Crespi" Istituto Di Ricovero e Cura a Carattere Scientifico, Istituto di Ricerche Farmacologiche "Mario Negri," Bergamo 24020, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Todeschini
authors.forename: Monica
authors.initials: M
authors.lastname: Cortinovis
authors.forename: Norberto
authors.initials: N
authors.lastname: Perico
authors.forename: Francesca
authors.initials: F
authors.lastname: Poli
authors.forename: Annalisa
authors.initials: A
authors.lastname: Innocente
authors.forename: Regiane Aparecida
authors.initials: RA
authors.lastname: Cavinato
authors.forename: Eliana
authors.initials: E
authors.lastname: Gotti
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
authors.forename: Flavio
authors.initials: F
authors.lastname: Gaspari
authors.forename: Marina
authors.initials: M
authors.lastname: Noris
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.forename: Federica
authors.initials: F
authors.lastname: Casiraghi
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology* / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000276:immunology / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D000077552:Basiliximab; D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D008212:Lymphocyte Depletion / Q000379:methods; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D006649:Histocompatibility Antigens; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000074323:Alemtuzumab; D000077552:Basiliximab