*Purpose: The need for extended high-resolution (HR) HLA genotyping in solid organ transplantation is currently widely debated due to higher costs and questioned clinical importance. Here we evaluated the impact of different HLA genotyping levels on the assignment of the presence of DSA. Additionally, we investigated whether imputation of HR genotypes based on low-resolution (LR) genotypes could be used to correctly assign the presence of DSA.

*Methods: We included 1000 single kidney transplant pairs transplanted in one center between 2004 and 2014, initially typed at LR split antigen level. The presence of anti-HLA antibodies was assessed by Luminex. The whole cohort was retyped at HR level for 11 HLA loci using NGS. HR HLA imputation was performed using HaploStats.

*Results: We detected pretransplant anti-HLA antibodies in 262/1000 recipients. Based on LR HLA typing donor data, serology or SSP for HLA-A/B/C/DRB1/DQB1, and Sanger sequencing for DPB1, pretransplant DSA were identified in 140 patients and absent in 860 patients (DSA_neg group). With extended HLA typing data of both donors and patients, we confirmed the presence of DSA in 108/140 (77.1%) patients (HR_posLR_posDSA group) and excluded DSA in 32/140 patients (22.9%) (HR_negLR_posDSA group). Kaplan-Meier curves showed that 10-year graft survival rates were similar between the DSA_neg and HR_negLR_posDSA groups (82.4% vs. 93.8%; p=0.27), which were both significantly better than graft survival in the HR_posLR_posDSA group (62.3%; p<0.001) (Figure1A). The main reasons for DSA misclassification were lack of 2^nd field donor typing 23/40 (57.5%), incomplete typing of the donor 10/40 (25.0%), and incomplete typing of the patient 7/40 (17.5%). Analyzed per HLA molecule, the majority of misclassified DSAs were against DQ 18/40 (45.0%). Finally, when we used imputed HR HLA typing results, we found that in 19/23 (82.6%) of the misclassified DSA that required 2^nd field HLA typing results of HR_negLR_posDSA group DSA could be correctly assigned by imputation. However, when we analyzed the presence of DSA in HR_posLR_posDSA group using imputed results, in 20/108 (18.5%) patients, DSA would be wrongly excluded (imputedDSA_neg) (Figure1B).

*Conclusions: Our study illustrates that extended HR HLA typing of the donor-recipient pairs is needed for correct assessment of DSA. Although imputation of HR genotypes from LR typing improves the assessment of DSA, significant misclassification occurs, and warrants caution in using imputed HLA results for clinical and research purposes.

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