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 |
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| Affiliation: | 1. Department of Medicine, Mayo Clinic, Phoenix, Arizona;2. Norton Thoracic Institute, St Joseph''s Hospital and Medical Center, Phoenix, Arizona;3. Department of Laboratory Medicine and Pathology, Mayo Clinic, Phoenix, Arizona;1. Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan;2. Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan;1. Department of Surgery, Tulane University School of Medicine, New Orleans, Louisiana;2. Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana;3. Department of Surgery, Weill Cornell Medicine, New York, New York;4. Tulane Transplant Institute, New Orleans, Louisiana;1. Department of Thoracic Surgery, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan;2. Department of Thoracic Surgery, Fujita Health University, Toyoake, Japan;3. Department of Pathology, Tohoku University, Sendai, Japan;4. Department of Pathology, Sendai Medical Center, Sendai, Japan;5. Department of Pediatrics, Tohoku University Hospital, Sendai, Japan;6. Division of Pediatrics, Tohoku Medical and Pharmaceutical University, Sendai, Japan;1. Urology Unit, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy;2. HPB and Transplant Surgery Unit, Department of Surgical Sciences, University of Rome Tor Vergata, Rome, Italy;1. University of California San Diego, Department of Internal Medicine, La Jolla, California;2. University of California San Diego, Department of Internal Medicine: Division of Pulmonology, La Jolla, California;3. University of California San Diego, Department of Surgery: Division of Cardiothoracic Surgery, La Jolla, California;4. University of California San Diego, Department of Internal Medicine: Division of Cardiovascular Diseases, La Jolla, California;5. University of California San Diego, Department of Pathology, La Jolla, California |
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| 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. |
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