HUMAN LEUKOCYE ANTIGEN (HLA)-DQA AND DQB EPLET MISMATCHES AND DE NOVO DONOR-SPECIFIC ANTI-HLA-DQ ANTIBODY

S FIDLER¹, L D’ORSOGNA¹, A IRISH², WH LIM³

¹ Department of Clinical Immunology, Fiona Stanley Hospital, Perth; ² Department of Renal Medicine, Fiona Stanley Hospital, Perth; ³ Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth

Aim: To determine the association between HLA-DQA and DQB eplet mismatches and development of de novo donor-specific anti-HLA-DQ antibody (DQ-DSA).

Background: DQ-DSA is the most common de novo DSA occurring post-kidney transplantation, often associated with an increased risk of antibody-mediated rejection and premature allograft loss. Even though HLA-DQ comprises of DQA1 and DQB1 gene products, DQA1 is not routinely typed in donor kidney allocation.

Methods: High-resolution molecular typing at the HLA-DQ allele in a cohort of 264 donor/recipient pairs in Western Australia between 2003-07 was performed using Sanger sequencing technique, with eplet mismatches calculated using HLAMatchmaker. Association between eplet mismatches at the HLA-DQA and HLA-DQB alleles and de novo DQ-DSA with mean fluorescent intensity of >500 (Luminex) was examined using logistic regression. Accuracy of eplet mismatches at the HLA-DQA and HLA-DQB alleles in predicting DQ-DSA was determined by Receiver Operating Characteristics Area Under the curve (AUC).

Results: Of the 264 recipients, 60 (23%) developed class II DSA, with 44/60 (73%) being DQ-DSA. The median (25-75th quartiles) number of eplet mismatches at the HLA-DQA and DQB alleles were 5 (0-15) and 9 (1-13), respectively. Every 5 additional eplet mismatches at the HLA-DQA locus was associated with an adjusted odds ratio of 1.43 (95%CI 1.09-1.87), compared to 1.16 (95%CI 0.83-1.62) for HLA-DQB locus. AUC for HLA-DQA eplet mismatches in predicting DQ-DSA was higher compared to HLA-DQB eplet mismatches (0.69 vs. 0.65; p=0.23).

Conclusions: There is a stronger association between HLA-DQA eplet mismatches and development of DQ-DSA compared to HLA-DQB mismatches. This study suggests that donor/recipient HLA-DQA typing should be routinely performed prior to kidney transplantation.