Prediction of HLA-DQ in Deceased Donors and its Clinical Significance in Kidney Transplantation

Abstract

Background HLA-DQ typing in deceased donors is not mandatory in Korea. Therefore, when patients develop DQ antibodies after kidney transplantation (KT) from deceased donor, it is impossible to determine whether they are donor-specific antibodies (DSA). We developed DQ prediction programs for the HLA gene and evaluated their clinical utility. Methods Two HLA-DQ prediction programs were developed one based on Lewontin’s linkage disequilibrium (LD) and haplotype frequency and the other on an artificial neural network (ANN). Low-resolution HLA-A, -B, -DR, and -DQ typing data of 5,603 Korean patients were analyzed in terms of haplotype frequency and used to develop an ANN DQ prediction program. Predicted DQ (pDQ) genotype accuracy was analyzed using the typed DQ data of 403 patients. pDQ DSA agreement, sensitivity, specificity, and false-negative rate was evaluated using 1,970 single-antigen bead assays performed on 885 KT recipients. The clinical significance of DQ and pDQ 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.

Donor-derived cell-free DNA predicted allograft rejection and severe microvascular inflammation in kidney transplant recipients

“…Application of Luminex single antigen (LSA) assay for the detection of donor-specific anti-HLA antibody has led to remarkable advances in minimally invasive biomarker development ( 2 ). Accumulating evidence has revealed that donor-specific anti-HLA antibody (DSA) plays a critical role in the progression of antibody-mediated allograft tissue injury, which in turn, is the most important cause of late allograft failure in KTRs ( 3 – 5 ). Therefore, detection and monitoring of DSA may help in predicting allograft outcomes and planning proper management to prevent decline of allograft function in KTRs ( 6 , 7 ).…”