TY - JOUR
T1 - Significance of HLA-DQ in kidney transplantation
T2 - time to reevaluate human leukocyte antigen–matching priorities to improve transplant outcomes? An expert review and recommendations
AU - Tambur, Anat R.
AU - Kosmoliaptsis, Vasilis
AU - Claas, Frans H.J.
AU - Mannon, Roslyn B.
AU - Nickerson, Peter
AU - Naesens, Maarten
N1 - Funding Information:
ART is a Paul I. Terasaki Scholar. VK acknowledges funding from an National Institute of Health Research (NIHR) Fellowship (PDF-2016-09-065) and from a P.I. Terasaki Scholarship. RBM is the chair of the Policy and Advocacy Committee of the American Society of Nephrology, but this article represents personal, not societal, views. PN is a Paul I. Terasaki Scholar. MN is senior clinical investigator of The Research Foundation Flanders (F.W.O.; 1844019N).
Funding Information:
ART is a Paul I. Terasaki Scholar. VK acknowledges funding from a National Institute of Health Research (NIHR) Fellowship (PDF-2016-09-065) and from a P.I. Terasaki Scholarship. RBM is the chair of the Policy and Advocacy Committee of the American Society of Nephrology, but this article represents personal, not societal, views. PN is a Paul I. Terasaki Scholar. MN is senior clinical investigator of The Research Foundation Flanders (F.W.O.; 1844019N).
Publisher Copyright:
© 2021 International Society of Nephrology
PY - 2021/11
Y1 - 2021/11
N2 - The weight of human leukocyte antigen (HLA) matching in kidney allocation algorithms, especially in the United States, has been devalued in a stepwise manner, supported by the introduction of modern immunosuppression. The intent was further to reduce the observed ethnic/racial disparity, as data emerged associating HLA matching with decreased access to transplantation for African American patients. In recent years, it has been increasingly recognized that a leading cause of graft loss is chronic antibody-mediated rejection, attributed to the development of de novo antibodies against mismatched donor HLA expressed on the graft. These antibodies are most frequently against donor HLA-DQ molecules. Beyond their impact on graft survival, generation of de novo donor-specific HLA antibodies also leads to increased sensitization, as measured by panel-reactive antibody metrics. Consequently, access to transplantation for patients returning to the waitlist in need of a second transplant is compromised. Herein, we address the implications of reduced HLA matching policies in kidney allocation. We highlight the observed diminished outcome data, the significant financial burden, the long-term health consequences, and, more important, the unintended consequences. We further provide recommendations to examine the impact of donor-recipient HLA class II and specifically HLA-DQα1β1 mismatching, focusing on collection of appropriate data, application of creative simulation approaches, and reconsideration of best practices to reduce inequalities while optimizing patient outcomes.
AB - The weight of human leukocyte antigen (HLA) matching in kidney allocation algorithms, especially in the United States, has been devalued in a stepwise manner, supported by the introduction of modern immunosuppression. The intent was further to reduce the observed ethnic/racial disparity, as data emerged associating HLA matching with decreased access to transplantation for African American patients. In recent years, it has been increasingly recognized that a leading cause of graft loss is chronic antibody-mediated rejection, attributed to the development of de novo antibodies against mismatched donor HLA expressed on the graft. These antibodies are most frequently against donor HLA-DQ molecules. Beyond their impact on graft survival, generation of de novo donor-specific HLA antibodies also leads to increased sensitization, as measured by panel-reactive antibody metrics. Consequently, access to transplantation for patients returning to the waitlist in need of a second transplant is compromised. Herein, we address the implications of reduced HLA matching policies in kidney allocation. We highlight the observed diminished outcome data, the significant financial burden, the long-term health consequences, and, more important, the unintended consequences. We further provide recommendations to examine the impact of donor-recipient HLA class II and specifically HLA-DQα1β1 mismatching, focusing on collection of appropriate data, application of creative simulation approaches, and reconsideration of best practices to reduce inequalities while optimizing patient outcomes.
KW - HLA matching
KW - HLA-DQ
KW - antibody-mediated rejection
KW - kidney transplantation
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U2 - 10.1016/j.kint.2021.06.026
DO - 10.1016/j.kint.2021.06.026
M3 - Review article
C2 - 34246656
AN - SCOPUS:85116037969
SN - 0085-2538
VL - 100
SP - 1012
EP - 1022
JO - Kidney International
JF - Kidney International
IS - 5
ER -