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Potential Implication of HLA-DQ Heterodimer High-Resolution Ty** on Kidney Transplant Outcomes and Equity

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Abstract

Purpose of Review

To evaluate the potential implications of HLA-DQαβ heterodimer high-resolution ty** on clinical decision-making in solid organ transplantation.

Recent Finding

Lack of HLA-DQαβ heterodimer high-resolution ty** information impacts cPRA calculations for patients on the waitlist and thus can affect their priority in organ allocation algorithms. It can further affect the number of potential compatible organ offers that they can receive.

Summary

We believe that the compiled data highlight the need for a thorough evaluation by the OPTN/UNOS, to assure equity for patients in need of organ transplantation.

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References 

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  1. Terasaki PI, Vredevoe DL, Porter KA, Mickey MR, Marchioro TL, Faris TD, Herrmann TJ, Starzl TE. Seroty** for homotransplantation V. Evaluation of a matching scheme. Transplantation. 1966;4 . https://doi.org/10.1097/00007890-196611000-00004.

  2. Vredevoe P, Terasaki M, Micke R, Glassock J, Merrill J, Murray. Seroty** of human lymphocyte antigens. III. Long term kidney homograft survivors. In: Amos D, Van Rood J, Editors. Histocompatibility Testing. Munksgaard: Copenhagen; 1965. p. 25–35.

  3. Takemoto S, Terasaki PI, Cecka JM, Cho YW, Gjertson DW. Survival of nationally shared, HLA-matched kidney transplants from cadaveric donors. New England J Med. 1992;327. https://doi.org/10.1056/nejm199209173271202.

  4. Roberts JP, Wolfe RA, Bragg-Gresham JL, Rush SH, Wynn JJ, Distant DA, Ashby VB, Held PJ, Port FK. Effect of changing the priority for HLA matching on the rates and outcomes of kidney transplantation in minority groups. New Engl J Med. 2004;350. https://doi.org/10.1056/nejmoa025056.

  5. Bodmer WF. The HLA system: structure and function. J Clin Pathol. 1987;40:948.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hurley CK, Naming HLA. Diversity: a review of HLA nomenclature. Hum Immunol. 2021;82. https://doi.org/10.1016/j.humimm.2020.03.005.

  7. Tiercy JM, Jeannet M, Mach B. A new approach for the analysis of HLA class II polymorphism: “HLA oligoty**.” Blood Rev. 1990;4. https://doi.org/10.1016/0268-960X(90)90012-H.

  8. Barker DJ, Maccari G, Georgiou X, Cooper MA, Flicek P, Robinson J, Marsh SGE. The IPD-IMGT/HLA database. Nucleic Acids Res. 2023;51. https://doi.org/10.1093/nar/gkac1011.

  9. Iniotaki-Theodoraki AG, Boletis JN, Trigas GC, Kalogeropoulou HG, Kostakis AG, Stavropoulos-Giokas CG. Humoral immune reactivity against human leukocyte antigen (HLA)-DQ graft molecules in the early posttransplantation period. Transplantation. 2023;75.https://doi.org/10.1097/01.TP.0000061611.51612.09.

  10. Ozawa M, Rebellato LM, Terasaki PI, Tong A, Briley KP, Catrou P, Haisch CE. Longitudinal testing of 266 renal allograft patients for HLA and MICA antibodies: Greenville experience. Clin Transpl. 2006.

  11. Freitas MCS, Rebellato LM, Ozawa M, Nguyen A, Sasaki N, Everly M, Briley KP, Haisch CE, Bolin P, Parker K, Kendrick WT, Kendrick SA, Harland RC, Terasaki PI. The role of immunoglobulin-G subclasses and C1q in de novo HLA-DQ donor-specific antibody kidney transplantation outcomes. Transplantation. 2013;95. https://doi.org/10.1097/TP.0b013e3182888db6.

  12. Tagliamacco A, Cioni M, Comoli P, Ramondetta M, Brambilla C, Trivelli A, Magnasco A, Biticchi R, Fontana I, Dulbecco P, Palombo D, Klersy C, Ghiggeri GM, Ginevri F, Cardillo M, Nocera A. DQ molecules are the principal stimulators of de novo donor-specific antibodies in nonsensitized pediatric recipients receiving a first kidney transplant. Transp Int. 2014;27. https://doi.org/10.1111/tri.12316.

  13. Wiebe C, Gibson IW, Blydt-Hansen TD, Karpinski M, Ho J, Storsley LJ, Goldberg A, Birk PE, Rush DN, Nickerson PW. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Trans. 2012;12. https://doi.org/10.1111/j.1600-6143.2012.04013.x.

  14. Everly MJ, Rebellato LM, Haisch CE, Ozawa M, Parker K, Briley KP, Catrou PG, Bolin P, Kendrick WT, Kendrick SA, Harland RC, Terasaki PI. Incidence and impact of de novo donor-specific alloantibody in primary renal allografts. Transplantation. 2013;95. https://doi.org/10.1097/TP.0b013e31827d62e3.

  15. • Willicombe M, Brookes P, Sergeant R, Santos-Nunez E, Steggar C, Galliford J, McLean A, Cook TH, Cairns T, Roufosse C, Taube D. De novo DQ donor-specific antibodies are associated with a significant risk of antibody-mediated rejection and transplant glomerulopathy. Transplantation. 2012;94. https://doi.org/10.1097/TP.0b013e3182543950. This work provides the most thorough and well-controlled evidence for the role of HLA-DQ antibodies in different transplant outcome parameters.

  16. Devos JM, Gaber AO, Knight RJ, Land GA, Suki WN, Gaber LW, Patel SJ. Donor-specific HLA-DQ antibodies may contribute to poor graft outcome after renal transplantation. Kidney Int. 2012;82. https://doi.org/10.1038/ki.2012.190.

  17. Lee H, Min JW, Il Kim J, Moon IS, Park KH, Yang CW, Chung BH, Oh EJ. Clinical significance of HLA-DQ antibodies in the development of chronic antibody-mediated rejection and allograft failure in kidney transplant recipients. Medicine (United States). 2016;95. https://doi.org/10.1097/MD.0000000000003094.

  18. Ticehurst EH, Molina MR, Frank R, Kearns J, Lal P, Goldberg LR, Tsai D, Wald J, Kamoun M. Antibody-mediated rejection in heart transplant patients: long-term follow up of patients with high levels of donor-directed anti-DQ antibodies. Clin Transpl. 2011. https://doi.org/10.1016/j.humimm.2011.07.138.

    Article  PubMed  Google Scholar 

  19. Lim WH, Chapman JR, Coates PT, Lewis JR, Russ GR, Watson N, Holdsworth R, Wong G. HLA-DQ mismatches and rejection in kidney transplant recipients. Clin J Ame Soc Nephrol. 2016;11. https://doi.org/10.2215/CJN.11641115.

  20. Leeaphorn N, APena JR, Thamcharoen N, Khankin EV, Pavlakis M, Cardarelli F. HLA-DQ mismatching and kidney transplant outcomes. Clin J Am Soc Nephrol. 2018;13 . https://doi.org/10.2215/CJN.10860917.

  21. Ting YT, Dahal-Koirala S, Kim HSK, Qiao SW, Neumann RS, Lundin KEA, Petersen J, Reid HH, Sollid LM, Rossjohn J. A molecular basis for the T cell response in HLA-DQ2.2 mediated celiac disease. Proc Natl Acad Sci USA. 2020;117. https://doi.org/10.1073/pnas.1914308117.

  22. • Isaacson D, Schold JD, Gmeiner MW, Copley HC, Kosmoliaptsis V, Tambur AR. HLA-DQ mismatches lead to more unacceptable antigens, greater sensitization, and increased disparities in repeat transplant candidates. J Am Soc Nephrol. 2022;33. https://doi.org/10.1681/ASN.2022030296. This work won the Best of the ASN Journals award in 2022. It provides the first demonstration of a functional association between recipient/donor HLA-DQ mismatching and the presence of donor specific antibodies post graft loss as well as its impact on elevated cPRA values.

  23. AR Tambur, JR Leventhal, JJ Friedewald, DS Ramon. The complexity of human leukocyte antigen (HLA) - DQ antibodies and its effect on virtual crossmatching. 90, 1117–1124 (2010).

  24. Tambur AR, Leventhal JR, Walsh RC, Zitzner JR, Friedewald JJ. HLA-DQ barrier: effects on cPRA calculations. Transplantation. 2013;96. https://doi.org/10.1097/TP.0b013e3182a452a5.

  25. Tambur AR, Leventhal JR, Zitzner JR, Carlin Walsh R, Friedewald JJ. The DQ barrier: improving organ allocation equity using HLA-DQ information. Transplantation. 2013;95. https://doi.org/10.1097/TP.0b013e318277b30b.

  26. Tambur AR, Audry B, Antoine C, Suberbielle C, Glotz D, Jacquelinet C. Harnessing Scientific and technological advances to improve equity in kidney allocation policies. Am J Transpl. 2017;17. https://doi.org/10.1111/ajt.14389.

  27. Kransdorf EP, Pando MJ, Stewart D, Lindblad K, Bray R, Murphey C, Kaur N, Patel JK, Kim I, Zhang X, Maiers M, Kobashigawa JA, Gragert L. Stem cell donor HLA ty** improves CPRA in kidney allocation. Am J Transpl.2021;21. https://doi.org/10.1111/ajt.16156.

  28. Keith DS, Vranic GM. Approach to the highly sensitized kidney transplant candidate. Clin J Am Soc Nephrol. 2016;11. https://doi.org/10.2215/CJN.05930615.

  29. Kransdorf EP, Pando MJ. Calculated panel reactive antibody with decimals: a refined metric of access to transplantation for highly sensitized candidates. Hum Immunol. 2017;78. https://doi.org/10.1016/j.humimm.2016.12.009.

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Acknowledgements

Anat R. Tambur is a Paul I. Terasaki Scholar.

Funding

Some of this work was funded by a generous contribution from the Paul I. Terasaki Memorial Research Fund.

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Authors and Affiliations

  1. Comprehensive Transplant Center, Department of Surgery, Northwestern University, Chicago, IL, USA

    Chelsea Maguire & Anat R. Tambur

  2. Feinberg School of Medicine, Northwestern University, 300 E Superior Ave, Tarry Building Suite 11-711, Chicago, IL, 60611-3008, USA

    Anat R. Tambur

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  1. Chelsea Maguire
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Correspondence to Anat R. Tambur.

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Maguire, C., Tambur, A.R. Potential Implication of HLA-DQ Heterodimer High-Resolution Ty** on Kidney Transplant Outcomes and Equity. Curr Transpl Rep 10, 230–236 (2023). https://doi.org/10.1007/s40472-023-00407-3

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