title: An analysis of lymphocyte phenotype after steroid avoidance with either alemtuzumab or basiliximab induction in renal transplantation.
abstract: Several studies have analyzed the phenotype of repopulated T-lymphocytes following alemtuzumab induction; however there has been less scrutiny of the reconstituted B-cell compartment. In the context of a randomized controlled trial (RCT) comparing alemtuzumab induction with tacrolimus monotherapy against basiliximab induction with tacrolimus and mycophenolate mofetil (MMF) therapy in renal transplantation, we analyzed the peripheral B- and T-lymphocyte phenotypes of patients at a mean of 25 +/- 2 months after transplantation. We examined the relationship between peripheral lymphocyte phenotype and graft function. Patients who received alemtuzumab had significantly higher numbers of B cells including naïve, transitional and regulatory subsets. In contrast, the CD4(+)  T-cell compartment was dominated by a memory cell phenotype. Following either basiliximab or alemtuzumab induction patients with lower numbers of B cells or B subsets had significantly worse graft function. For alemtuzumab there was also a correlation between these subsets the stability of graft function and the presence of HLA-specific antibodies. These results demonstrate that a significant expansion of regulatory type B cells is associated with superior graft function and that this pattern is more common after alemtuzumab induction. This phenomenon requires further prospective study to see whether this phenotype could be used to customize immunotherapy.
authors.affiliation: Renal Transplant Unit, University of Leeds, Leeds, UK. drcherukuri2102@doctors.org.uk
authors.forename: A
authors.initials: A
authors.lastname: Cherukuri
authors.forename: A D
authors.initials: AD
authors.lastname: Salama
authors.forename: C
authors.initials: C
authors.lastname: Carter
authors.forename: N
authors.initials: N
authors.lastname: Smalle
authors.forename: R
authors.initials: R
authors.lastname: McCurtin
authors.forename: E W
authors.initials: EW
authors.lastname: Hewitt
authors.forename: M
authors.initials: M
authors.lastname: Hernandez-Fuentes
authors.forename: B
authors.initials: B
authors.lastname: Clark
authors.forename: R J
authors.initials: RJ
authors.lastname: Baker
mesh_terms: D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000077552:Basiliximab; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008214:Lymphocytes / Q000276:immunology*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000074323:Alemtuzumab; D000077552:Basiliximab; D009173:Mycophenolic Acid; D016559:Tacrolimus