Aim: Allele-specific HLA antibodies are commonly detected by Luminex single antigen bead assays in solid organ transplant recipients. However, high-resolution HLA typing for deceased donors is usually unavailable. This causes uncertainty in reporting donor-specific antibodies and virtual crossmatching. Therefore, we investigated the ability of haplotype analysis to predict high-resolution HLA-A, -B, -C, -DRB1 and -DQB1 and low-resolution HLA-DQA1 typing from low-resolution HLA-A, -B, -C, -DRB1 and -DQB1 typing and its possible application for virtual crossmatching.

Methods: Haplotypes (n=270) from proficiency testing samples (n=135), with known low- and high-resolution typing results, were analyzed based on data compiled from the NMDP registry database (Maiers M, et al. Human Immunology 2007; 68: 779) and the ethnic background of the sample. Low-resolution HLA typing (-A, -B, -C, -DRB1 and -DQB1) was entered in a haplotype analysis tool and the predicted high-resolution typing was compared to the actual results. Subsequently, using the high-resolution HLA-DRB1 and HLA-DQB1 typing, we predicted the low-resolution HLA-DQA1 typing based on common HLA-DRB1, -DQA1 and -DQB1 allele associations (Fernandez-Viña M, et al. Immunogenetics 1991; 34: 299) and compared to the actual results.

Results: The haplotype analysis tool correctly predicted high-resolution HLA typing 87% of the time with the highest prediction rate for HLA-C (90%) and HLA-DQB1 (90%) and the lowest for HLA-DRB1 (82%) (Table 1). In addition, the predicted typing rate for HLA-DQA1 was 95% (Table 1).

Conclusion: Haplotype analysis based on common allele associations is an accurate method to predict high-resolution HLA-A, -B, -C, -DRB1 and -DQB1 typing and low-resolution HLA-DQA1 typing. This method allows for identification of allele-specific donor-specific antibodies with greater accuracy and further aids in solid organ allocation as well as post-transplant management of sensitized patients.

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