A SHARMA1,2, A TAVERNITI1, HTD NGUYEN3,4, RJ DUQUESNOY5, JR LEWIS1-4, A IRISH6, L D’ORSORGNA7, J CRAIG1,2, G WONG1,2, WH LIM3,4.
1Centre for Kidney Research, Children’s Hospital at Westmead, Westmead, NSW; 2School of Public Health, Sydney Medical School, The University of Sydney, Sydney, NSW; 3School of Medicine and Pharmacology, University of Western Australia, Perth, WA; 4Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, WA; 5University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 6Department of Renal Medicine, Fiona Stanley Hospital, Perth, WA; 7Department of Clinical Immunology, Fiona Stanley Hospital, Perth, WA
Aim: To investigate if Indigenous renal transplant recipients have novel HLA alleles and to compare the number of eplet mismatches at HLA ABDRB1 loci between Indigenous and Caucasian renal transplant recipients.
Background: Indigenous renal transplant recipients are more likely to receive donor kidneys with a greater number of broad antigen HLA-mismatches, which is likely to contribute to the higher rates of rejection and allograft loss compared to Caucasian recipients. Eplet mismatches have been shown to improve immunological risk assessment, including predicting acute rejection and development of anti-HLA antibodies. Novel HLA alleles are likely to be present in Indigenous people, which are likely to affect the accurate determination of eplet mismatches.
Methods: The number of eplet mismatches was calculated using HLAMatchmaker. The two sample t-test was used to compare the mean number of HLA and eplet mismatches between Indigenous and Caucasian recipients.
Results: 329 (51 Indigenous, 278 Caucasian) adult deceased donor recipients between 2000-2011 in Western Australia were included. The mean number of HLA mismatches at ABDRB1 for Indigenous recipients (4.1, SD1.7) was higher than for Caucasian recipients (2.8, SD1.4) (t327=-5.71, P<0.01). The mean number of eplet mismatches at ABDRB1 for Indigenous recipients (27.5, SD13.4) was also higher than for Caucasian recipients (18.8, SD10.7) (t327=-5.13, P<0.01). Seventeen novel alleles (6 at HLA-AB, 11 at HLA-DRB1) were identified at the HLA-ABDRB1 loci.
Conclusions: The recognition of novel HLA alleles is important to more accurately determine the extent of broad antigen and eplet HLA mismatches between donors and Indigenous recipients. Future research incorporating these novel alleles into the HLAMatchmaker program and to investigate the relationship between eplet mismatches and allograft outcome in this cohort is required.