Significance of HLA-DQ in kidney transplantation: time to reevaluate human leukocyte antigen–matching priorities to improve transplant outcomes? An expert review and recommendations

Anat R. Tambur*, Vasilis Kosmoliaptsis, Frans H.J. Claas, Roslyn B. Mannon, Peter Nickerson, Maarten Naesens

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1012-1022
Number of pages11
JournalKidney international
Volume100
Issue number5
DOIs
StatePublished - Nov 2021

Keywords

  • HLA matching
  • HLA-DQ
  • antibody-mediated rejection
  • kidney transplantation

ASJC Scopus subject areas

  • Nephrology

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