Circulating B Cells with Memory and Antibody-Secreting Phenotypes Are Detectable in Pediatric Kidney Transplant Recipients Before the Development of Antibody-Mediated Rejection

Abstract

Development of anti-HLA donor specific antibodies (DSA) is associated with antibody mediated rejection (AMR) and reduced allograft survival. Whether changes in lymphocytes anticipate DSA or AMR is unclear. We used CyTOF to analyze peripheral blood mononuclear cells (PBMC) from pediatric kidney transplant recipients who developed DSA (DSA^POS, n=10). PBMC were obtained at 2 months post-transplant, 3 months prior to DSA and at DSA detection. PBMC collected at the same timepoints from recipients that did not develop DSA (DSA^NEG, n=11) were used as controls. Within DSA^POS recipients, there was no difference in DSA levels, C1q-, or C3d-binding between patients who developed AMR and those who did not. However, DSAPOS patients that developed AMR had increased B cells with antibody-secreting (IgD^-CD27⁺CD38⁺; p=0.002) and memory (IgD^-CD27⁺CD38^-; p=0.003) phenotypes. Our analyses show that B cells with memory and antibody-secreting phenotypes are present more than 1 year prior to AMR in pediatric kidney transplant recipients.