In this single-center matched-cohort study, we evaluated the phenotype of repopulating B cells and its correlation with donorspecific anti-HLA Ab development and long-term graft function in 16 renal transplant recipients and 32 age- and gendermatched 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.
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 / M. Todeschini, M. Cortinovis, N. Perico, F. Poli, A. Innocente, R.A. Cavinato, E. Gotti, P. Ruggenenti, F. Gaspari, M. Noris, G. Remuzzi, F. Casiraghi. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 191:5(2013), pp. 2818-2828. [10.4049/jimmunol.1203261]
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
G. RemuzziPenultimo
;
2013
Abstract
In this single-center matched-cohort study, we evaluated the phenotype of repopulating B cells and its correlation with donorspecific anti-HLA Ab development and long-term graft function in 16 renal transplant recipients and 32 age- and gendermatched 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.File | Dimensione | Formato | |
---|---|---|---|
J Immunol-2013-Todeschini-2818-28.pdf
accesso riservato
Tipologia:
Publisher's version/PDF
Dimensione
2.06 MB
Formato
Adobe PDF
|
2.06 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.