As there were some inaccuracies in the prediction programs developed in this study, a policy of HLA-DQ typing for deceased donors should be established as promptly as you possibly can in Korea. == ACKNOWLEDGEMENTS == None. == Footnotes == AUTHOR CONTRIBUTIONS HO designed the study; SKK and JJY collected and analyzed the data; SKK wrote the paper; SH, HS, SS and SYK contributed to the conception. DSA was evaluated in 411 KT recipients. == Results == pDQ genotype accuracies were 75.4% (LD algorithm) and 75.7% (ANN). When the second most likely pDQ (LD algorithm) was also considered, the genotype accuracy increased to 92.6%. pDQ DSA (LD algorithm) agreement, sensitivity, specificity, and falsenegative rate were 97.5%, 97.3%, 98.6%, and 2.4%, respectively. The antibody-mediated rejection treatment frequency was significantly higher in DQ or pDQ DSA-positive patients than in DQ or pDQ DSA-negative patients (P< 0.001). == Conclusions == Our DQ prediction programs showed good accuracy and could aid DQ DSA detection in patients who had undergone deceased donor KT without donor HLA-DQ typing. Keywords:Artificial neural network, Donor-specific antibody, HLA-DQ, Kidney transplantation, Linkage disequilibrium == INTRODUCTION == The clinical significance of HLA-DQ antibodies in kidney transplantation (KT) has been highlighted by the development of molecular HLA typing and single-antigen bead (SAB) assay. It is known that 15%30% of patients develop donor-specific antibodies (DSA) within three years of KT, and 33%77% of them develop DQ DSA, which is usually associated with poor graft outcome [17]. Given its clinical significance, HLA-DQ typing for deceased donors is required by Eurotransplant (Austria, Belgium, Croatia, Germany, Hungary, Luxembourg, the Netherlands, and Slovenia) and the United Network for Organ Sharing (USA) [8,9]. However, HLA-DQ typing for deceased donors is not yet required in Korea. Furthermore, the Korean Network for Organ Sharing has no regulations regarding deceased donor specimen storage for additional HLA typing, making retrospective HLA typing nearly impossible. Therefore, when a patient develops DQ antibodies after deceased Rabbit Polyclonal to CDCA7 donor KT, it is impossible to determine whether these antibodies are donor-specific or not. HLA shows common haplotype characteristics according to individual ethnic groups [10,11]. Therefore, HLA-DQ can be predicted using HLA haplotype frequency and linkage disequilibrium (LD) data. We developed a DQ prediction program based on HLA-A, -B, and -DR and analyzed the clinical significance of the predicted DQ (pDQ) in KT recipients. To the best of our knowledge, this is the first study to predict HLA-DQ using an artificial neural network (ANN) and to evaluate its clinical significance. == MATERIALS GSK3368715 AND METHODS == == Data source and study populace == HLA typing data, SAB assay data, and patients medical records were retrospectively reviewed. To develop the DQ prediction program and evaluate its accuracy, low-resolution HLA-A, -B, -C, -DR, -DQ typing data of 6,006 Korean patients registered at Asan Medical Center, Seoul, Korea from October 2005 to April 2019 were used. The data of 5,603 patients were analyzed in terms of allele and haplotype frequencies and used to train an ANN. The data of the remaining 403 patients were used to evaluate the accuracy of the HLA-DQ prediction program (Fig. 1A). == Fig. 1. == Patient GSK3368715 and data selection flowchart. (A) HLA-DQ prediction program development and evaluation. (B) Evaluation of pDQ DSA agreement, sensitivity, and specificity. (C) Evaluation of DQ and pDQ DSA clinical significance. Abbreviations: ANN, artificial neural network; DSA, donor specific antibody; KT, kidney transplantation; LD, linkage disequilibrium; pDQ, predicted DQ; SAB, single-antigen bead. To evaluate pDQ DSA agreement, sensitivity, specificity, and clinical significance, we enrolled Korean patients who underwent KT between January 2008 and December 2017, whose recipient/donor HLA-A, -B, -DR typing data were available, and who had undergone follow-up class I and II SAB assays. Patients who underwent kidney re-transplantation or any other type of transplantation were excluded. A total of 1 1,567 patients met the inclusion criteria. For pDQ DSA agreement, sensitivity, and specificity analyses, recipients/donors with unknown HLA-DQ were excluded. In total, 885 recipients/donors with available HLA-DQ typing GSK3368715 data were included (Fig. 1B). To evaluate the clinical significance of pDQ DSA, previously selected 1,567 patients were divided into the deceased donor KT and living donor KT groups. The deceased donor KT group (N = 319) was subdivided according to donor HLA-DQ availability and DQ or pDQ DSA positivity. In the living donor KT group (N = 1,248), 92 patients who had ABO-compatible KT in 2013 were selected and subdivided according to DQ DSA positivity (Fig..
As there were some inaccuracies in the prediction programs developed in this study, a policy of HLA-DQ typing for deceased donors should be established as promptly as you possibly can in Korea