Impact of HLA eplet mismatch load in immunological outcomes after living donor kidney transplantation |
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| Affiliation: | 1. Faculty of Medical Sciences, Belo Horizonte, Minas Gerais, Brazil;2. University Hospital of the Faculty of Medical Sciences, Belo Horizonte, Minas Gerais, Brazil;3. IMUNOLAB – Laboratory of Histocompatibility, Belo Horizonte, Minas Gerais, Brazil;4. Institute of Research and Education of the Hospital Santa Casa, Belo Horizonte, Minas Gerais, Brazil;1. Biology Department, Science and Arts University, Yazd, Iran;2. Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;3. Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;4. Department of Biological Sciences, Faculty of Engineering and Science, Science and Arts University, Yazd, Iran;1. Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA;2. Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States of America;3. Department of Pharmacy Practice, College of Pharmacy, University of Rhode Island, Kingston, RI, USA;1. Department of Transfusion Medicine, Histocompatibility and Molecular Biology, Jaypee Hospital, Noida, UP 201301, India;2. Department of Histocompatibility and Molecular Biology, Jaypee Hospital, Noida,UP 201301, India;3. Department of Transfusion Medicine, Jaypee Hospital, Noida, UP 201301, India;4. Kidney Transplant Programme, Department of Urology and Kidney Transplant, Jaypee Hospital, Noida, UP 201301, India;5. Department of Nephrology and Kidney Transplant, Jaypee Hospital, Noida, UP 201301, India;1. Renal Department, St James''s University Hospital, Leeds, United Kingdom;2. NIHR Leeds In-Vitro Diagnostics Co-operative, Leeds, United Kingdom;3. Histocompatibility and Immunogenetics, NHS Blood and Transplant, Birmingham, United Kingdom;4. Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom |
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| Abstract: | IntroductionHLA eplets mismatches (eMM) have been associated with negative kidney outcomes after transplantation, such as the development of de novo donor-specific antibody (dnDSA), antibody-mediated rejection (ABMR), and early graft loss. This study aimed to evaluate the clinical effects of the HLA eMM load on dnDSA development, ABMR, renal function, allograft survival and graft loss.Material and methodsThis retrospective study involved 159 living donor kidney transplant patients categorized into groups based on antigen HLA mismatches assessed traditionally and HLA eMM load. Patients had followed for at least one year. The EpViX online program was used to evaluate the HLA eMM load. Cox models were constructed to assess the risk of graft loss. Kaplan-Meier survival curves were carried out. The analyses had performed using the R program and p < 0.05 was considered significant.ResultsFrom all 159 patients, 28 (17.6%) lost their allografts. Rejection episodes occurred in 37.1% of patients, 13.6% of whom were ABMR. Patients with rejection episodes had higher HLA-AB (p = 0.032) and HLA-DR (p = 0.008) HLA eMM load, HLA-AB (p = 0.006) and HLA-DR (p = 0.009) antigens mismatches, and higher proportions of the following eMM in the HLA-DR locus: 70R eMM (p = 0.015), 70RE (p = 0.015), 74E (p = 0.015) and 48Q (p = 0.047). In multiple models, the presence of HLA-DR 70qq eMM (HR 3.75, 95% CI 1.47; 9.55) add an increase in creatinine levels at 1-year (HR 3.87, 95% CI 2.30, 6.53) were associated with the risk of graft loss.ConclusionThe HLA eMM load was related to episodes of rejection and allograft loss. The HLA-DR eMM was most strongly associated with a worse immunologic outcome than eMM mismatches for HLA-AB. |
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