Low Hydrophobic Mismatch Scores Calculated for HLA-A/B/DR/DQ Loci Improve Kidney Allograft Survival

Dulat Bekbolsynov; Beata Mierzejewska; Jadwiga Borucka; Robert S. Liwski; Anna L. Greenshields; Joshua Breidenbach; Bradley Gehring; Shravan Leonard-Murali; Sadik A. Khuder; Michael Rees; Robert C. Green; Stanislaw M. Stepkowski

doi:10.3389/fimmu.2020.580752

Low Hydrophobic Mismatch Scores Calculated for HLA-A/B/DR/DQ Loci Improve Kidney Allograft Survival

Dulat Bekbolsynov, Beata Mierzejewska, Jadwiga Borucka, Robert S. Liwski, Anna L. Greenshields, Joshua Breidenbach, Bradley Gehring, Shravan Leonard-Murali, Sadik A. Khuder, Michael Rees, Robert C. Green, Stanislaw M. Stepkowski

Medicine

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9 Citas (Scopus)

Resumen

We evaluated the impact of human leukocyte antigen (HLA) disparity (immunogenicity; IM) on long-term kidney allograft survival. The IM was quantified based on physicochemical properties of the polymorphic linear donor/recipient HLA amino acids (the Cambridge algorithm) as a hydrophobic, electrostatic, amino acid mismatch scores (HMS\AMS\EMS) or eplet mismatch (EpMM) load. High-resolution HLA-A/B/DRB1/DQB1 types were imputed to calculate HMS for primary/re-transplant recipients of deceased donor transplants. The multiple Cox regression showed the association of HMS with graft survival and other confounders. The HMS integer 0–10 scale showed the most survival benefit between HMS 0 and 3. The Kaplan–Meier analysis showed that: the HMS=0 group had 18.1-year median graft survival, a 5-year benefit over HMS>0 group; HMS ≤ 3.0 had 16.7-year graft survival, a 3.8-year better than HMS>3.0 group; and, HMS ≤ 7.8 had 14.3-year grafts survival, a 1.8-year improvement over HMS>7.8 group. Stratification based on EMS, AMS or EpMM produced similar results. Additionally, the importance of HLA-DR with/without -DQ IM for graft survival was shown. In our simulation of 1,000 random donor/recipient pairs, 75% with HMS>3.0 were re-matched into HMS ≤ 3.0 and the remaining 25% into HMS≥7.8: after re-matching, the 13.5 years graft survival would increase to 16.3 years. This approach matches donors to recipients with low/medium IM donors thus preventing transplants with high IM donors.

Idioma original	English
Número de artículo	580752
Publicación	Frontiers in Immunology
Volumen	11
DOI	https://doi.org/10.3389/fimmu.2020.580752
Estado	Published - oct. 29 2020

Nota bibliográfica

Funding Information:
Research reported in this publication was supported by the National Library of Medicine of the National Institutes of Health under Award Number R01LM013311 as part of the NSF/NLM Generalizable Data Science Methods for Biomedical Research Program. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional funding was provided by The Alliance for Paired Donation, Maumee, OH, USA.

Funding Information:
The data reported here have been supplied by the Minneapolis Medical Research Foundation (MMRF) as the contractor for the Scientific Registry of Transplants Recipients (SRTR). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the SRTR or the U.S. Government. Notably, the principles of the Helsinki Declaration were followed.

Publisher Copyright:
© Copyright © 2020 Bekbolsynov, Mierzejewska, Borucka, Liwski, Greenshields, Breidenbach, Gehring, Leonard-Murali, Khuder, Rees, Green and Stepkowski.

ASJC Scopus Subject Areas

Immunology and Allergy
Immunology

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Bekbolsynov, D., Mierzejewska, B., Borucka, J., Liwski, R. S., Greenshields, A. L., Breidenbach, J., Gehring, B., Leonard-Murali, S., Khuder, S. A., Rees, M., Green, R. C., & Stepkowski, S. M. (2020). Low Hydrophobic Mismatch Scores Calculated for HLA-A/B/DR/DQ Loci Improve Kidney Allograft Survival. Frontiers in Immunology, 11, Artículo 580752. https://doi.org/10.3389/fimmu.2020.580752

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title = "Low Hydrophobic Mismatch Scores Calculated for HLA-A/B/DR/DQ Loci Improve Kidney Allograft Survival",

abstract = "We evaluated the impact of human leukocyte antigen (HLA) disparity (immunogenicity; IM) on long-term kidney allograft survival. The IM was quantified based on physicochemical properties of the polymorphic linear donor/recipient HLA amino acids (the Cambridge algorithm) as a hydrophobic, electrostatic, amino acid mismatch scores (HMS\AMS\EMS) or eplet mismatch (EpMM) load. High-resolution HLA-A/B/DRB1/DQB1 types were imputed to calculate HMS for primary/re-transplant recipients of deceased donor transplants. The multiple Cox regression showed the association of HMS with graft survival and other confounders. The HMS integer 0–10 scale showed the most survival benefit between HMS 0 and 3. The Kaplan–Meier analysis showed that: the HMS=0 group had 18.1-year median graft survival, a 5-year benefit over HMS>0 group; HMS ≤ 3.0 had 16.7-year graft survival, a 3.8-year better than HMS>3.0 group; and, HMS ≤ 7.8 had 14.3-year grafts survival, a 1.8-year improvement over HMS>7.8 group. Stratification based on EMS, AMS or EpMM produced similar results. Additionally, the importance of HLA-DR with/without -DQ IM for graft survival was shown. In our simulation of 1,000 random donor/recipient pairs, 75% with HMS>3.0 were re-matched into HMS ≤ 3.0 and the remaining 25% into HMS≥7.8: after re-matching, the 13.5 years graft survival would increase to 16.3 years. This approach matches donors to recipients with low/medium IM donors thus preventing transplants with high IM donors.",

author = "Dulat Bekbolsynov and Beata Mierzejewska and Jadwiga Borucka and Liwski, {Robert S.} and Greenshields, {Anna L.} and Joshua Breidenbach and Bradley Gehring and Shravan Leonard-Murali and Khuder, {Sadik A.} and Michael Rees and Green, {Robert C.} and Stepkowski, {Stanislaw M.}",

note = "Funding Information: Research reported in this publication was supported by the National Library of Medicine of the National Institutes of Health under Award Number R01LM013311 as part of the NSF/NLM Generalizable Data Science Methods for Biomedical Research Program. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional funding was provided by The Alliance for Paired Donation, Maumee, OH, USA. Funding Information: The data reported here have been supplied by the Minneapolis Medical Research Foundation (MMRF) as the contractor for the Scientific Registry of Transplants Recipients (SRTR). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the SRTR or the U.S. Government. Notably, the principles of the Helsinki Declaration were followed. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2020 Bekbolsynov, Mierzejewska, Borucka, Liwski, Greenshields, Breidenbach, Gehring, Leonard-Murali, Khuder, Rees, Green and Stepkowski.",

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AU - Bekbolsynov, Dulat

AU - Mierzejewska, Beata

AU - Borucka, Jadwiga

AU - Liwski, Robert S.

AU - Greenshields, Anna L.

AU - Breidenbach, Joshua

AU - Gehring, Bradley

AU - Leonard-Murali, Shravan

AU - Khuder, Sadik A.

AU - Rees, Michael

AU - Green, Robert C.

AU - Stepkowski, Stanislaw M.

N1 - Funding Information: Research reported in this publication was supported by the National Library of Medicine of the National Institutes of Health under Award Number R01LM013311 as part of the NSF/NLM Generalizable Data Science Methods for Biomedical Research Program. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional funding was provided by The Alliance for Paired Donation, Maumee, OH, USA. Funding Information: The data reported here have been supplied by the Minneapolis Medical Research Foundation (MMRF) as the contractor for the Scientific Registry of Transplants Recipients (SRTR). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the SRTR or the U.S. Government. Notably, the principles of the Helsinki Declaration were followed. Publisher Copyright: © Copyright © 2020 Bekbolsynov, Mierzejewska, Borucka, Liwski, Greenshields, Breidenbach, Gehring, Leonard-Murali, Khuder, Rees, Green and Stepkowski.

PY - 2020/10/29

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N2 - We evaluated the impact of human leukocyte antigen (HLA) disparity (immunogenicity; IM) on long-term kidney allograft survival. The IM was quantified based on physicochemical properties of the polymorphic linear donor/recipient HLA amino acids (the Cambridge algorithm) as a hydrophobic, electrostatic, amino acid mismatch scores (HMS\AMS\EMS) or eplet mismatch (EpMM) load. High-resolution HLA-A/B/DRB1/DQB1 types were imputed to calculate HMS for primary/re-transplant recipients of deceased donor transplants. The multiple Cox regression showed the association of HMS with graft survival and other confounders. The HMS integer 0–10 scale showed the most survival benefit between HMS 0 and 3. The Kaplan–Meier analysis showed that: the HMS=0 group had 18.1-year median graft survival, a 5-year benefit over HMS>0 group; HMS ≤ 3.0 had 16.7-year graft survival, a 3.8-year better than HMS>3.0 group; and, HMS ≤ 7.8 had 14.3-year grafts survival, a 1.8-year improvement over HMS>7.8 group. Stratification based on EMS, AMS or EpMM produced similar results. Additionally, the importance of HLA-DR with/without -DQ IM for graft survival was shown. In our simulation of 1,000 random donor/recipient pairs, 75% with HMS>3.0 were re-matched into HMS ≤ 3.0 and the remaining 25% into HMS≥7.8: after re-matching, the 13.5 years graft survival would increase to 16.3 years. This approach matches donors to recipients with low/medium IM donors thus preventing transplants with high IM donors.

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Low Hydrophobic Mismatch Scores Calculated for HLA-A/B/DR/DQ Loci Improve Kidney Allograft Survival

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ASJC Scopus Subject Areas

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