B lymphocyte biomarker analysis to risk-stratify clinical outcomes in renal allograft recipients

There is increasing interest in understanding how the immune phenotype may be associated with allograft outcomes, and efforts are being made to identify biomarkers that can predict outcome and guide clinical management. This report describes the evaluation of potential biomarkers associated with the B-cell phenotype. Firstly, an observational study using UK registry data was undertaken to compare the medium-term outcomes of adult recipients of their first renal transplant receiving either alemtuzumab or basiliximab. This study concluded that alemtuzumab induction permits steroid avoidance in significantly higher numbers of patients without any obvious penalty. The effect of both induction agents on the B-cell phenotype was studied prospectively in a cohort of adult renal transplant recipients, with time-dependent alterations assessed against clinical outcomes. In particular, the immunomodulatory function of B-cells was explored within the transitional B-cell (TrB) population as this has been demonstrated to contain high concentrations of regulatory B-cells. Changes within TrB subsets were found to be associated with rejection and reduced graft survival. CD9 expression was also investigated to determine its value in highlighting regulatory B-cells (Bregs). Increased expression was demonstrated within TrBs including those producing IL-10, however it was not an exclusive marker for Bregs.

Secondly, B-cells as antibody producers were assessed. Two assays to determine the presence of alloreactive memory B-cells were considered. The first assay involved the non-specific stimulation of peripheral blood mononuclear cells (PBMCs) into antibody secreting cells, with the collection of cell supernatant for the assessment of HLA antibodies. The second method aimed to quantify alloreactive B-cells through the co-incubation of PBMCs with single antigen beads. Finally, a retrospective study of HLA-DP antibody incompatible renal transplants was carried out; findings demonstrate that these transplants should be considered high risk, and laboratory tests cannot further risk stratify these patients.