An Enhanced Role of Innate Immunity in the Immune Response After Kidney Transplant in People Living With HIV: A Transcriptomic Analysis

Abstract

Background. Although kidney transplantation (KT) has become the standard of care for people living with HIV (PLWH) suffering from renal failure, early experiences revealed unanticipated higher rejection rates than those observed in HIV− recipients. The cause of increased acute rejection (AR) in PLWH was assessed by performing a transcriptomic analysis of biopsy specimens, comparing HIV+ to HIV− recipients. Methods. An analysis of 68 (34 HIV+, 34 HIV−) formalin-fixed paraffin-embedded (FFPE) renal biopsies matched for degree of inflammation was performed from KT recipients with acute T cell-mediated rejection (aTCMR), borderline for aTCMR (BL), and normal findings. Gene expression was measured using the NanoString platform on a custom gene panel to assess differential gene expression (DE) and pathway analysis (PA). Results. DE analysis revealed multiple genes with significantly increased expression in the HIV+ cohort in aTCMR and BL relative to the HIV− cohort. PA of these genes showed enrichment of various inflammatory pathways, particularly innate immune pathways associated with Toll-like receptors. Conclusions. Upregulation of the innate immune pathways in the biopsies of PLWH with aTCMR and BL is suggestive of a unique immune response that may stem from immune dysregulation related to HIV infection. These findings suggest that these unique HIV-driven pathways may in part be contributory to the increased incidence of allograft rejection after renal transplantation in PLWH.