Impact of Solvent-Accessible HLA Amino Acid Mismatches on Kidney Transplant Outcomes: A Multicenter Longitudinal Study Article Swipe

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Soufian Meziyerh , Suzanne Bezstarosti , Aleksandar Senev , Dennis A. J. van den Broek , Maarten Coemans , Jesper Kers , Teun van Gelder , Danny van der Helm , Paul van der Boog , Johan W. de Fijter , Abeer Madbouly , Dirk Jan A. R. Moes , Cees van Kooten , Gonca E. Karahan , Geert W. Haasnoot , Marie‐Paule Emonds , Maarten Naesens , Sebastiaan Heidt , Dave L. Roelen , Aiko P. J. de Vries ·

YOU? · · 2025 · Open Access · · DOI: https://doi.org/10.21203/rs.3.rs-7115262/v1

Current alloimmune risk assessment in kidney transplantation relies on HLA antigen mismatches, lacking precision for individualized care. In contrast, solvent-accessible HLA amino acid (saAA) mismatches, empirically defined across all HLA loci, offer a stable and objective alternative. We conducted a multicenter longitudinal study evaluating saAA mismatches, calculated using HLA-EMMA, in relation to key transplant outcomes. Among 2,473 kidney transplant recipients (median follow-up 6.9 years), 36% reached a hierarchical composite endpoint of death-censored graft failure(DCGF), biopsy-proven acute rejection(BPAR), or de novo donor-specific antibody(dnDSA). Multivariable analyses showed total, class I, class II, and locus-specific saAA mismatch scores were significantly associated with the composite outcome, as well as DCGF, BPAR and dnDSA individually (all P<.001). These findings suggest that saAA mismatch load provides a more granular and reproducible measure of alloimmune risk compared to traditional antigen-level mismatches. Incorporating saAA mismatch analysis could enable personalized immunosuppression strategies and optimized transplant monitoring in clinical practice.

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Randomized Controlled Trial

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Kidney transplant Human leukocyte antigen Solvent Multicenter study Longitudinal study Amino acid Longitudinal data Kidney transplantation Kidney Medicine Chemistry Internal medicine Computer science Biochemistry Immunology Data mining Pathology Antigen Randomized controlled trial

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Type: preprint
Language: en
Landing Page: https://doi.org/10.21203/rs.3.rs-7115262/v1
PDF: https://www.researchsquare.com/article/rs-7115262/latest.pdf
OA Status: gold
References: 44
Related Works: 10
OpenAlex ID: https://openalex.org/W4412516356

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DOI: https://doi.org/10.21203/rs.3.rs-7115262/v1

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Title: Impact of Solvent-Accessible HLA Amino Acid Mismatches on Kidney Transplant Outcomes: A Multicenter Longitudinal Study

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Type: preprint

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Language: en

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Publication year: 2025

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Publication date: 2025-07-21

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Authors: Soufian Meziyerh, Suzanne Bezstarosti, Aleksandar Senev, Dennis A. J. van den Broek, Maarten Coemans, Jesper Kers, Teun van Gelder, Danny van der Helm, Paul van der Boog, Johan W. de Fijter, Abeer Madbouly, Dirk Jan A. R. Moes, Cees van Kooten, Gonca E. Karahan, Geert W. Haasnoot, Marie‐Paule Emonds, Maarten Naesens, Sebastiaan Heidt, Dave L. Roelen, Aiko P. J. de Vries

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Landing page: https://doi.org/10.21203/rs.3.rs-7115262/v1

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Concepts: Kidney transplant, Human leukocyte antigen, Solvent, Multicenter study, Longitudinal study, Amino acid, Longitudinal data, Kidney transplantation, Kidney, Medicine, Chemistry, Internal medicine, Computer science, Biochemistry, Immunology, Data mining, Pathology, Antigen, Randomized controlled trial

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