HLA-DQ Mismatches and Rejection in Kidney Transplant Recipients

Abstract

Background and objectives: The current allocation algorithm for deceased donor kidney transplantation takes into consideration HLA mismatches at the ABDR loci but not HLA mismatches at other loci, including HLA-DQ. However, the independent effects of incompatibilities for the closely linked HLA-DQ antigens in the context of HLA-DR antigen matched and mismatched allografts are uncertain. We aimed to determine the effect of HLA-DQ mismatches on renal allograft outcomes.

Design, setting, participants, & measurements: Using data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the association between HLA-DQ mismatches and acute rejections in primary live and deceased donor kidney transplant recipients between 2004 and 2012 using adjusted Cox regression models.

Results: Of the 788 recipients followed for a median of 2.8 years (resulting in 2891 person-years), 321 (40.7%) and 467 (59.3%) received zero and one or two HLA-DQ mismatched kidneys, respectively. Compared with recipients who have received zero HLA-DQ mismatched kidneys, those who have received one or two HLA-DQ mismatched kidneys experienced greater numbers of any rejection (50 of 321 versus 117 of 467; P<0.01), late rejections (occurring >6 months post-transplant; 8 of 321 versus 27 of 467; P=0.03), and antibody-mediated rejections (AMRs; 12 of 321 versus 38 of 467; P=0.01). Compared with recipients of zero HLA-DQ mismatched kidneys, the adjusted hazard ratios for any and late rejections in recipients who had received one or two HLA-DQ mismatched kidneys were 1.54 (95% confidence interval [95% CI], 1.08 to 2.19) and 2.85 (95% CI, 1.05 to 7.75), respectively. HLA-DR was an effect modifier between HLA-DQ mismatches and AMR (P value for interaction =0.02), such that the association between HLA-DQ mismatches and AMR was statistically significant in those who have received one or two HLA-DR mismatched kidneys, with adjusted hazard ratio of 2.50 (95% CI, 1.05 to 5.94).

Conclusions: HLA-DQ mismatches are associated with acute rejection, independent of HLA-ABDR mismatches and initial immunosuppression. Clinicians should be aware of the potential importance of HLA-DQ matching in the assessment of immunologic risk in kidney transplant recipients.

Keywords: Allografts; Epidemiology and outcomes; HLA Antigens; HLA-matching; Humans; acute allograft rejection; immunosuppression; kidney transplantation; registry; renal dialysis.

Figure 1.

Incidence and forest plots of the adjusted hazard ratios of timing and types of acute rejection after kidney transplantation stratified by HLA-DQ matched and mismatched kidney transplants adjusted for donor and recipient age, race, donor type, body mass index, era, number of HLA-ABDR mismatches, panel reactive antibody, waiting time, ischemic time, induction therapy, and initial immunosuppression. *Interaction between HLA-DQ and HLA-DR mismatches with adjusted hazard ratio of one or two HLA-DQ mismatches compared to zero HLA-DQ mismatch for zero and one or two HLA-DR mismatched kidneys; ^#incidence of antibody mediated rejection in recipients of zero HLA-DR and one or two HLA-DQ mismatched kidneys, and one or two HLA-DR and one or two HLA-DQ mismatched kidneys. 95% CI, 95% confidence interval.

Figure 2.

Adjusted cumulative incidence curves for any rejection after kidney transplantation according to HLA-DQ matched and mismatched kidney transplants (log rank P value <0.01). MM, mismatched.

Figure 3.

Adjusted cumulative incidence curves for antibody-mediated rejection after kidney transplantation according to HLA-DQ matched and mismatched kidney transplants (log rank P value <0.01). MM, mismatched.