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Terasaki Epitope Mismatch Burden Predicts the Development of De Novo DQ Donor-Specific Antibodies and are Associated With Adverse Allograft Outcomes

Willicombe, Michelle, MD, MA, MRCP1; Blow, Matthew, BSc2; Santos-Nunez, Eva, MSc2; Freeman, Corinna, MSc2; Brookes, Paul, PhD2; Taube, David, FRCP1

doi: 10.1097/TP.0000000000001887
Original Clinical Science—General

Background De novo DQ donor-specific antibody (DSA) are associated with antibody-mediated rejection and allograft loss. Given the lack of effective treatment of de novo DQ DSA, their prevention is vital if there is to be an improvement of long-term allograft survival. Using the HLA Matchmaker program, DQ epitope matching has been shown to be superior to HLA antigen mismatching in predicting de novo DQ DSA development. Whether DQ epitopes determined by Terasaki may more accurately predict de novo DQ development over HLA antigen matching is not known.

Methods We retrospectively analyzed the immunogenicity of the different HLA antigens, DQB1 alleles and DQB1 Teraskai epitopes (TerEp) in a large cohort of renal transplant recipients, by comparing patient mismatches with de novo DSA development.

Results Patients mismatched at a DQB1 allele were at significantly higher risk of developing de novo DSA compared with other mismatched HLA antigens. Patients mismatched at the DQ7 allele appear to be at specific risk. For patients mismatched at a single DQB1 allele, the risk of de novo DQ DSA development increases with the number of TerEp mismatches. However, the immunogenicity of the different DQ TerEps does not appear to be equal. Patients who develop antibodies against TerEps are at increased risk of adverse allograft outcomes, specifically antibody-mediated rejection.

Conclusions Epitope mismatch burden, determined by TerEps, helps predict risk of de novo DQ DSA development and offers an alternative approach to predict an alloimmune response.

In a large cohort of kidney transplant recipients, the authors demonstrate that Terasaki epitope mismatching at the DQB1 lead to an increased incidence of de novo HLA-DQ donor-specific antibodies and antibody-mediated rejection.

1 Imperial College Renal and Transplant Centre, Hammersmith Hospital, London, United Kingdom.

2 Histocompatibility and Immunogenetics Laboratory, Imperial College Healthcare NHS Trust, London, United Kingdom.

Received 28 October 2016. Revision received 5 June 2017.

Accepted 20 June 2017.

The authors declare no funding or conflicts of interest.

M.W. participated by collecting and analyzing clinical data along with writing the article. M.B., E.S., C.F. and P.B. participated by generating and analyzing the epitope data and reviewing the written article. D.T. participated by reviewing the written article.

Correspondence: Michelle Willicombe, MA, MRCP, MD, 4th Floor Ham House, Hammersmith Hospital London W12 0HS, United Kingdom. (Michelle.Willicombe@imperial.nhs.uk).

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

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