B cell reconstitution following alemtuzumab induction under a belatacept-based maintenance regimen.

Abstract

Lymphocyte depletion has been shown to control costimulation blockade-resistant rejection but, in some settings, to exacerbate antibody-mediated rejection (AMR). We have used alemtuzumab, which depletes T and B cells, combined with belatacept and rapamycin and previously reported control of both costimulation blockade-resistant rejection and AMR. To evaluate this regimen's effect on B cell signatures, we investigated 40 patients undergoing this therapy. B cell counts and phenotypes were interrogated using flow cytometry, and serum was analyzed for total IgG, IgM, and donor-specific alloantibody (DSA). Alemtuzumab induction produced pan-lymphocyte depletion; B cells repopulated faster and more completely than T cells. Reconstituting B cells were predominantly naïve, and memory B cells were significantly reduced (P=.001) post repopulation. Two B cell populations with potential immunomodulatory effects-regulatory (CD38hi CD24hi IgMhi CD20hi ) and transitional B cells (CD19+ CD27- IgD+ CD38hi )-were enriched posttransplant (P=.001). Total serum IgG decreased from baseline (P=.016) while IgM levels remained stable. Five patients developed DSAs within 36months posttransplant, but none developed AMR. Baseline IgG levels in these patients were significantly higher than those in patients without DSAs. These findings suggest that belatacept and rapamycin together limit homeostatic B cell activation following B cell depletion and may lessen the risk of AMR. This regimen warrants prospective, comparative study. ClinicalTrials.gov NCT00565773.