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.
Todeschini M, Cortinovis M, et al.Journal of Immunology 2013; 191(5): 2818-2828.
Aims
To evaluate the repopulating B cells and its correlation with donor-specific anti-HLA antibody(Ab) development and long term graft function in renal transplant recipients.
Interventions
Patients received alemtuzumab induction and an age and sex matched cohort received induction with basiliximab followed by low dose rabbit antithymocyte globulin for 5 days after transplantation. All patients received either low dose sirolimus or low dose cyclosporine together with mycophenolate mofetil as maintenance immunosuppression.
Participants
16 kidney transplant patients were induced with alemtuzumab and 32 age and sex matched participants were induced with basiliximab followed by rATG after transplantation.
Outcomes
The outcomes included glomerular filtration rate, peripheral B lymphocyte counts and phenotype, soluble BAFF and alemtuzumab assays, and anti-HLA Ab determination.
Follow-up
2 years.
CET Conclusions
This is a cohort study rather than a randomised controlled trial, although the subjects studied were part of an RCT, but is particularly interesting and hence is included in the Trial Watch. Sixteen renal transplant recipients received induction with Alemtuzumab and 32 age and sex matched controls were induced with Basiliximab and received low dose rabbit antithymocyte globulin for the first 5 days after transplantation. All patients received maintenance therapy with either low dose cyclosporine or low dose sirolimus and MMF. There was a marked difference in the phenotype of the B cell depletion and recovery in the two cohorts. In the BAS/ATG cohort there was no modification of the B cell phenotype while in the Alemtuzumab cohort there was a major dysregulation of reconstituted B cells and the significant development of donor specific antibodies after 1 and 2 years post-transplant. From this cohort study it would seem that the induction with Alemtuzumab produces profound and long lasting B cell depletion but with de novo chronic humoral responses (DSA) against the graft.
Quality notes
Quality assessement not applicable.
Trial registration
ClinicalTrials.gov - NCT00309270