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.
|Titolo:||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|
REMUZZI, GIUSEPPE (Penultimo)
|Parole Chiave:||regulatory T-cells; antithymocyte globulin; renal-transplantation; theumatoid-arthritis; multiple-sclerosis; excess baff; therapy; homeostasis; induction; identification|
|Settore Scientifico Disciplinare:||Settore MED/14 - Nefrologia|
|Data di pubblicazione:||2013|
|Digital Object Identifier (DOI):||10.4049/jimmunol.1203261|
|Appare nelle tipologie:||01 - Articolo su periodico|