Validation of a Novel Computational Approach for Predicting HLA Immunogenicity Based on Quantification of Structural and Surface Electrostatic Potential Differences Between Donor and Recipient HLA.
1Department of Surgery, University of Cambridge, Cambridge, United Kingdom
2University of Kiel, Kiel, Germany
3NHS Blood and Transplant, Bristol, United Kingdom
Meeting: 2017 American Transplant Congress
Abstract number: A130
Keywords: Alloantibodies, HLA antigens, HLA matching, Kidney transplantation
Session Information
Session Name: Poster Session A: Diagnostics/Biomarkers Session I
Session Type: Poster Session
Date: Saturday, April 29, 2017
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall D1
Background: Our preliminary work indicates that donor HLA immunogenicity in kidney and haematopoietic stem cell transplantation can be predicted by comparative assessment of donor and recipient amino-acid sequence and physicochemical properties. We have now created a novel computational algorithm to quantify structural and surface electrostatic potential differences between donor and recipient HLA and applied it to predict alloantibody responses in a unique patient cohort.
Methods: We examined 191 patients that underwent treatment for infertility with lymphocyte immunotherapy (LIT). Patients were injected intradermally with partner´s lymphocytes, and serum samples collected prior to and after LIT to assess HLA-specific sensitisation (Luminex single-antigen-beads). Following two field HLA typing, HLA structural modelling and calculation of HLA electrostatic potential, donor-recipient HLA comparisons were performed to determine the electrostatic mismatch score (EMS-3D) and assess its ability to predict donor-specific antibody (DSA) development and overall sensitisation to HLA post-LIT [expressed as calculated PRA (cPRA)].
Results: The EMS-3D of mismatched HLA ranged 0 to 0.488 (median: 0.268, IQR: 0.200-0.344). Increasing EMS-3D was strongly associated with higher risk of DSA development against HLA-A and -B (OR: 1.70 per 0.1 unit increase, 95%CI: 1.35-2.15, p<0.0001) and against HLA-DR and -DQ (OR: 2.35 per 0.1 unit increase, 95%CI: 1.94-2.84, p<0.0001). Notably, physicochemical differences between donor and recipient HLA-DQ were higher compared to other loci (EMS-3D median: 0.346, IQR: 0.200-0.421) and donor HLA-DQ with the highest EMS-3D (fourth quartile) were highly likely to induce a DSA response (OR: 30.8, 95%CI: 11.6-81.9, p<0.0001). The overall physicochemical disparity between donor and recipient HLA types was an independent predictor of the risk of developing high levels of sensitisation to HLA (cPRA≥85%, OR: 1.09 per 0.1 unit increase in EMS-3D, 95%CI: 1.01-1.17, p=0.02).
Discussion: Donor HLA immunogenicity can be predicted by computation of structural and physicochemical disparities with recipient HLA to enable better assessment of transplant immunological risk and help inform future deceased-donor kidney allocation policies.
CITATION INFORMATION: Kosmoliaptsis V, Kling C, Robb M, Collett D, Bradley J, Taylor C, Kabelitz D, Mallon D. Validation of a Novel Computational Approach for Predicting HLA Immunogenicity Based on Quantification of Structural and Surface Electrostatic Potential Differences Between Donor and Recipient HLA. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Kosmoliaptsis V, Kling C, Robb M, Collett D, Bradley J, Taylor C, Kabelitz D, Mallon D. Validation of a Novel Computational Approach for Predicting HLA Immunogenicity Based on Quantification of Structural and Surface Electrostatic Potential Differences Between Donor and Recipient HLA. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/validation-of-a-novel-computational-approach-for-predicting-hla-immunogenicity-based-on-quantification-of-structural-and-surface-electrostatic-potential-differences-between-donor-and-recipient-hla/. Accessed May 9, 2025.« Back to 2017 American Transplant Congress