Memory B-Cell Assay Uncovers Prior HLA Sensitisation in Transplant Candidates With Prior Exposure to Non-Self HLA

Memory B cells are critical in kidney transplantation for rapid anti-HLA antibody production upon re-exposure, yet pretransplant serum antibodies often remain undetectable despite prior sensitisation. Using R848 stimulation (a TLR7/8 agonist inducing polyclonal B-cell activation), we tested 45 kidney recipients with past sensitisation events but no circulating antibodies. The assay identified 56 memory B-cell-derived HLA antibodies (HLAm) in 8 patients, primarily from pregnancy or transfusion sensitisation, with a 17-year average latency between exposure and transplantation. This pilot demonstrates that latent memory B cells may reactivate post-transplant, driving antibody production and adverse outcomes. Our findings advocate integrating memory B-cell assays into pretransplant risk assessment to improve sensitivity in detecting subclinical HLA sensitisation, refining donor-recipient matching strategies.