Predictability of eplet mismatch to acute rejection in low level HLA antigen mismatched kidney transplantation: Validation analysis of Korean Organ Transplantation Registry (KOTRY) data
Jong Cheol Jeong1, Hyeong Eun Son1, Yeon Ho Park2, Inwhee Park3, Jae Berm Park4, Dong Wan Chae1,5, Jaeseok Yang6, Curie Ahn5, Yun Ji Hong7, Borae G. Park8.
1Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; 2Department of Surgery, Gachon University College of Medicine, Incheon, Korea; 3Department of Nephrology, Ajou University School of Medicine, Suwon, Korea; 4Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 5Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; 6Transplantation Center, Seoul National University Hospital, Seoul, Korea; 7Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; 8Department of Laboratory Medicine, College of Medicine, Korea University Guro Hospital, Seoul, Korea
KOTRY study group.
Introduction: Epitope matching has been shown to better predict allograft survival and development of de novo donor specific antibodies. In our previous study, the number of epitope matching was shown to have additional risk in the low level of HLA mismatch (HLA mismatch less than 3). We tried to assess whether the finding was validated in an external validation cohort.
Methods: Patients included in Korean Organ Transplantation Registry (KOTRY) were used. Kidney transplant recipients who have been transplanted from 2014 to 2017 were enrolled. As an external validation cohort, retrospective KOTRY data (kidney transplant pairs from 2009 to 2012) were used. HLA 4 digits genotype were imputed by matching to the 4 digits haplotype distribution in Korean bone marrow donor program. DQ genotyping were imputed by linkage-disequlibrium association. Primary outcome measurement was biopsy proven acute rejection.
Results: Among 5,872 donor-recipient pairs, 4 digits haplotype pairs were successfully imputed. Mean number of mismatched class I and class II eplet were 10.5 ± 6.8 (Range; 0 – 35) and 24.1 ± 17.4 (0 – 85), respectively. Mean eplet mismatch numbers were increased according to the number of HLA antigen mismatch (Beta 9.340, 95% C.I. 9.145 – 9.534, p<0.001). Eplet mismatch was associated with acute rejection in the unadjusted models. (Class I 1.022, 95% C.I. 1.011 – 1.033, p<0.001; Class II 1.011, 95% C.I. 1.007 – 1.015, p<0.001) When controlled with clinical covariates and HLA mismatch numbers, eplet mismatch numbers did not show additional predictability to acute rejection. (AUC comparison; eplet model vs. HLA serotype model, 0.615 (95% C.I 0.594 – 0.636) vs 0.619 (95% C.I. 0.598 – 0.640), p=0.491) However, eplet class II mismatches over 60 was shown to be significant risk predictors in the low HLA serotype mismatches (1 or 2 mismatches) in a non-linear model.
Conclusion: In this external validation study, eplet mismatches in class II MHC was found as significant risk factors to acute rejection in low degree HLA mismatches (1 or 2 mismatches).
This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention (code: 2014-ER6301-00, 2014-ER6301-01, 2014-ER6301-02, 2017-ER6301-00, 2017-ER6301-01, 2017-ER6301-02).
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