Adequate tacrolimus exposure modulates the impact of HLA class II molecular mismatch: a validation study in an American cohort

Am J Transplant. 2021 Jan;21(1):322-328. doi: 10.1111/ajt.16290. Epub 2020 Oct 11.


Clinicians have few tools to predict the risk of alloimmune injury that would guide immunosuppression management in renal transplant patients. We evaluated human leukocyte antigen (HLA)-DR/DQ molecular mismatch to predict de novo donor-specific antibodies (DSAs) during the first year of transplant and explored how differences in tacrolimus exposure may modulate this risk. HLA-DR and -DQ eplet mismatches were determined between 444 donor-recipient pairs in Denver, Colorado between 2007 and 2013. Previously defined mismatch thresholds stratified recipients into low- (N = 119), intermediate- (N = 153), and high- (N = 172) risk categories. The area under the curve for DSA at 1 year was 0.84 and 0.82 for HLA-DR and HLA-DQ eplet mismatches, respectively. Compared to low-risk patients, there was a graded increase in risk of DR/DQ DSA in intermediate (HR 15.39, 95% CI 2.01-118.09, p = .009) and high-risk (HR 23.81, 95% CI 3.17-178.66, p = 0.002) categories. Intermediate- and high-risk patients with a mean tacrolimus <6 ng/ml versus >8 ng/ml had increased risk of DR/DQ DSA at 1 year (HR 2.34, 95% CI 1.05-5.22, p = .04). HLA molecular mismatch represents a reproducible, objective, and clinically relevant tool to stratify patients by alloimmune risk and may help guide personalized immunosuppression management.

Keywords: alloantibody; autoimmunity; clinical research / practice; histocompatibility; immunosuppressant - calcineurin inhibitor: tacrolimus; immunosuppression / immune modulation; kidney transplantation / nephrology; monitoring: immune; rejection.

MeSH terms

  • Graft Rejection* / etiology
  • Graft Survival
  • HLA Antigens / genetics
  • HLA-DR Antigens
  • Histocompatibility Testing
  • Humans
  • Tacrolimus*
  • United States


  • HLA Antigens
  • HLA-DR Antigens
  • Tacrolimus