Date: Saturday, April 29, 2017
Session Name: Poster Session A: Diagnostics/Biomarkers Session I
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 October 1, 2020.
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