Immunological Mechanisms of Allograft Rejection Following Kidney Transplantation at Lagos University Teaching Hospital: A Translational Study

Kidney transplantation is the optimal treatment for end-stage renal disease, yet rejection rates in Nigerian patients remain high relative to international benchmarks, partly because immunological rejection profiles in Black African populations are not well characterized. This translational study investigates the cellular and molecular immunological mechanisms of allograft rejection in kidney transplant recipients at Lagos University Teaching Hospital (LUTH), Lagos State, South West Nigeria, from 2018 to 2023. Forty-five kidney transplant recipients were prospectively enrolled and underwent serial allograft biopsies at 3 months, 1 year, and 3 years. Biopsies were analyzed by histopathology (Banff classification), immunohistochemistry for CD4, CD8, CD20, and C4d, and donor-specific antibody (DSA) profiling by single antigen bead assay. T-cell mediated rejection occurred in 38% of patients, while antibody-mediated rejection was identified in 24%. De novo DSA formation was detected in 33% of patients, predominantly against HLA-DQ loci. HLA mismatch score and medication non-adherence were the strongest independent predictors of rejection. Regulatory T-cell dysfunction was identified as a novel mechanistic correlate of chronic antibody-mediated rejection in this cohort. The study provides translational insights that inform immunosuppression optimization strategies and recommends establishment of a dedicated transplant immunology laboratory at LUTH to enable personalized immunosuppression protocols. Keywords: kidney transplantation, allograft rejection, donor-specific antibody, immunology, LUTH