A Comparison of HLA Molecular Mismatch Methods to Determine HLA Immunogenicity.
Taylor, Craig J
Wolters Kluwer Health
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Wiebe, C., Kosmoliaptsis, V., Pochinco, D., Taylor, C. J., & Nickerson, P. (2018). A Comparison of HLA Molecular Mismatch Methods to Determine HLA Immunogenicity.. Transplantation, 102 (8), 1338-1343. https://doi.org/10.1097/tp.0000000000002117
Antibody-mediated rejection is a major cause of premature graft loss in kidney transplantation. Multiple scoring systems are available to assess the HLA mismatch between donors and recipients at the molecular level, however, their correlation with the development of de novo donor-specific antibody (dnDSA) has not been compared in recipients on active immunosuppression. Methods HLA-DRβ1/3/4/5/DQα1β1 molecular mismatch was determined using eplet analysis, amino acid mismatch, and electrostatic mismatch for 596 renal transplant recipients and correlated with HLA-DR/DQ dnDSA development. The molecular mismatch scores were evaluated in multivariate models of post-transplant dnDSA free survival. Results Eplet mismatch correlated with amino acid mismatch and electrostatic mismatch (R2=0.85-0.96). HLA-DR dnDSA free survival correlated with HLA-DR eplet mismatch (HR 2.50 per 10 eplets mismatched, p<0.0001), amino acid mismatch (HR 1.49 per 10 amino acids mismatched, p<0.0001), and electrostatic mismatch (HR 1.23 per 10 units mismatched, p<0.0001). HLA-DQ dnDSA free survival correlated with HLA-DQ eplet mismatch (HR 1.98 per 10 eplets mismatched, p<0.0001), amino acid mismatch (HR 1.24 per 10 amino acids mismatched, p<0.0001), and electrostatic mismatch (HR 1.14 per 10 units mismatched, p<0.0001). All three methods were significant multivariate correlates of dnDSA development after adjustment for recipient age, baseline immunosuppression, and non-adherence. Conclusion HLA molecular mismatch represents a precise method of alloimmune risk assessment for renal transplant patients. This report highlights that the use of one method over the other is likely to be driven by familiarity and ease of use as highly correlated results are produced by each method.
Humans, Kidney Failure, Chronic, Antibodies, HLA Antigens, Histocompatibility Testing, Disease-Free Survival, Immunosuppression, Kidney Transplantation, Multivariate Analysis, Proportional Hazards Models, Risk Assessment, Follow-Up Studies, Graft Survival, Adolescent, Adult, Middle Aged, Static Electricity, Young Adult
Evelyn Trust (14/25)
Academy of Medical Sciences (unknown)
Addenbrooke's Charitable Trust (ACT) (CT/03/16 B (vii))
Department of Health (via National Institute for Health Research (NIHR)) (NIHR-PDF-2016-09-065)
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External DOI: https://doi.org/10.1097/tp.0000000000002117
This record's URL: https://www.repository.cam.ac.uk/handle/1810/275000
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