Direct Correlation of Soluble HLA and HLA-Containing Exosomes and Inverse Correlation of Tolerance Marker-Containing Exosomes With Antibody-Mediated Rejection After Simultaneous Liver-Kidney Transplantation: A Case Study

Abstract

There is a lower incidence of antibody-mediated rejection (AMR) after simultaneous liver-kidney transplantation (SLKT) than after kidney-only transplantation. It has been suggested that soluble human leukocyte antigen (sHLA) produced by the liver protects the kidney from AMR. However, this hypothesis has not been tested after SLKT. We present a case of SLKT with 2 donor-specific antibodies (DSAs) (DR53, 12,364 mean fluorescence intensity [MFI]; DQ7, 1253 MFI) that displayed a decrease by day 7 (DR53, 2747 MFI; DQ7, 107 MFI). On day 351, the patient was diagnosed with kidney AMR associated with high levels of DSA (DR53, 18,542 MFI; DQ7, 22,007 MFI) that persisted until day 531. High levels of sHLA-DR/DQ and HLA-DR/DQ-containing exosomes were also detected on day 398. Consequently, the patient underwent treatment with plasmapheresis, intravenous immunoglobulin, prednisone, and rituximab. On day 752, biopsy results were negative for AMR. Moderate levels of DSA (DR53, 9798 MFI; DQ7, 1271 MFI), and baseline levels of sHLA-DR/DQ and HLA-DR/DQ-containing exosomes were observed. Increases in CD4⁺CD25⁺FOXP3⁺ regulatory T cell marker-containing exosomes (CD73, programmed death-ligand 1) were observed on day 752 compared to day 398. These data show a direct correlation between sHLA and HLA-containing exosomes and an inverse correlation between tolerance marker-containing exosomes and kidney AMR after SLKT.