HLA class, calcineurin inhibitor levels, and the risk of graft failure in kidney recipients with de novo donor-specific antibodies

Front Immunol. 2024 Nov 20:15:1493878. doi: 10.3389/fimmu.2024.1493878. eCollection 2024.

Abstract

Introduction: De novo donor-specific HLA antibody (dnDSA) are associated with poor outcomes. Whether this observation applies to both HLA class I and II dnDSA remains unclear.

Methods: We studied 1236 consecutive kidney recipients who had routine anti-HLA antibody surveillance post-transplant.

Results: During the screening period, 55/1236 (4.4%) patients developed dnDSA: 18 (33%) HLA-I only, 33 (60%) HLA-II only, and 4 (7%) both classes. Thirty patients experienced graft loss at a median of 39 months after dnDSA detection: 9/18 (50%) HLA-I only, 17/33 (52%) HLA-II only, and 4/4 (100%) both classes. A control group was created by matching patients with dnDSA to patients who did not develop DSA and had a functioning graft at the time of dnDSA detection in their respective cases. Compared with these controls, the risk estimates of graft loss were similar between patients with HLA-I only and HLA-II only dnDSA (aHR [95% CI] 2.7 [1.1-6.6], p=0.04 and 3.1 [1.5-6.6], p<0.01 respectively). Additionally, the risk of graft loss decreased with increasing CNI trough levels following dnDSA detection (aHR 0.7 [0.6-0.9] for each increase in 1 ng/mL, p=0.02).

Conclusions: The prognosis of patients with dnDSA is similar regardless of the HLA class specificity. Lower calcineurin inhibitor levels predict graft loss in such patients.

Keywords: HLA class 1; anti-HLA alloantibodies; donor-specific alloantibodies; graft loss; kidney transplantation.

MeSH terms

  • Adult
  • Aged
  • Calcineurin Inhibitors* / therapeutic use
  • Female
  • Graft Rejection* / blood
  • Graft Rejection* / immunology
  • Graft Survival / immunology
  • HLA Antigens / immunology
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Isoantibodies* / blood
  • Isoantibodies* / immunology
  • Kidney Transplantation* / adverse effects
  • Male
  • Middle Aged
  • Risk Factors
  • Tissue Donors*

Substances

  • Isoantibodies
  • Calcineurin Inhibitors
  • HLA Antigens
  • Histocompatibility Antigens Class I

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by an Operating Grant from the Canadian Institutes of Health Research (CIHR PJT-166018). SS was supported by a scholarship from the Fonds the Recherche Quebec Sante (FRQS 282015).