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The role of HLA-DP mismatches and donor specific HLA-DP antibodies in kidney transplantation : a case series

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Abstract
BACKGROUND: The impact of HLA-DP mismatches on renal allograft outcome is still poorly understood and is suggested to be less than that of the other HLA loci. The common association of HLA-DP donor-specific antibodies (DSA) with other DSA obviates the evaluation of the actual effect of HLA-DP DSA. METHODS: From a large multicenter data collection, we retrospectively evaluated the significance of HLA-DP DSA on transplant outcome and the immunogenicity of HLA-DP eplet mismatches with respect to the induction of HLA-DP DSA. Furthermore, we evaluated the association between the MFI of HLA-DP antibodies detected in Luminex assays and the outcome of flowcytometric/complement-dependent cytotoxicity (CDC) crossmatches. RESULTS: In patients with isolated pretransplant HLA-DP antibodies (N = 13), 6 experienced antibody-mediated rejection (AMR) and 3 patients lost their graft. In HLAMatchmaker analysis of HLA-DP mismatches (N = 72), HLA-DP DSA developed after cessation of immunosuppression in all cases with 84DEAV (N = 14), in 86% of cases with 85GPM (N = 6/7), in 50% of cases with 56E (N = 6/12) and in 40% of cases with 56A mismatch (N = 2/5). Correlation analysis between isolated HLA-DP DSA MFI and crossmatches (N = 90) showed negative crossmatch results with HLA-DP DSA MFI <2000 (N = 14). Below an MFI of 10,000 CDC crossmatches were also negative (N = 33). Above these MFI values both positive (N = 35) and negative (N = 16) crossmatch results were generated. CONCLUSIONS: Isolated HLA-DP DSA are rare, yet constitute a significant risk for AMR. We identified high-risk eplet mismatches that can lead to HLA-DP DSA formation. We therefore recommend HLA-DP typing to perform HLA-DP DSA analysis before transplantation. HLA-DP DSA with high MFI were not always correlated with positive crossmatch results.
Keywords
Crossmatch, Eplets., HLA-DP antibodies, Human leukocyte antigen, Renal transplantation

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MLA
Daniëls, L., et al. “The Role of HLA-DP Mismatches and Donor Specific HLA-DP Antibodies in Kidney Transplantation : A Case Series.” TRANSPLANT IMMUNOLOGY, vol. 65, 2021, doi:10.1016/j.trim.2020.101287.
APA
Daniëls, L., Claas, F., Kramer, C., Senev, A., Vanden Driessche, M., Edmonds, M., … Naessens, M. (2021). The role of HLA-DP mismatches and donor specific HLA-DP antibodies in kidney transplantation : a case series. TRANSPLANT IMMUNOLOGY, 65. https://doi.org/10.1016/j.trim.2020.101287
Chicago author-date
Daniëls, L, FHJ Claas, CSM Kramer, A Senev, M Vanden Driessche, MP Edmonds, Steven Van Laecke, R Hellemans, D Abramowicz, and M Naessens. 2021. “The Role of HLA-DP Mismatches and Donor Specific HLA-DP Antibodies in Kidney Transplantation : A Case Series.” TRANSPLANT IMMUNOLOGY 65. https://doi.org/10.1016/j.trim.2020.101287.
Chicago author-date (all authors)
Daniëls, L, FHJ Claas, CSM Kramer, A Senev, M Vanden Driessche, MP Edmonds, Steven Van Laecke, R Hellemans, D Abramowicz, and M Naessens. 2021. “The Role of HLA-DP Mismatches and Donor Specific HLA-DP Antibodies in Kidney Transplantation : A Case Series.” TRANSPLANT IMMUNOLOGY 65. doi:10.1016/j.trim.2020.101287.
Vancouver
1.
Daniëls L, Claas F, Kramer C, Senev A, Vanden Driessche M, Edmonds M, et al. The role of HLA-DP mismatches and donor specific HLA-DP antibodies in kidney transplantation : a case series. TRANSPLANT IMMUNOLOGY. 2021;65.
IEEE
[1]
L. Daniëls et al., “The role of HLA-DP mismatches and donor specific HLA-DP antibodies in kidney transplantation : a case series,” TRANSPLANT IMMUNOLOGY, vol. 65, 2021.
@article{8656403,
  abstract     = {{BACKGROUND:
The impact of HLA-DP mismatches on renal allograft outcome is still poorly understood and is suggested to be less than that of the other HLA loci. The common association of HLA-DP donor-specific antibodies (DSA) with other DSA obviates the evaluation of the actual effect of HLA-DP DSA.

METHODS:
From a large multicenter data collection, we retrospectively evaluated the significance of HLA-DP DSA on transplant outcome and the immunogenicity of HLA-DP eplet mismatches with respect to the induction of HLA-DP DSA. Furthermore, we evaluated the association between the MFI of HLA-DP antibodies detected in Luminex assays and the outcome of flowcytometric/complement-dependent cytotoxicity (CDC) crossmatches.

RESULTS:
In patients with isolated pretransplant HLA-DP antibodies (N = 13), 6 experienced antibody-mediated rejection (AMR) and 3 patients lost their graft. In HLAMatchmaker analysis of HLA-DP mismatches (N = 72), HLA-DP DSA developed after cessation of immunosuppression in all cases with 84DEAV (N = 14), in 86% of cases with 85GPM (N = 6/7), in 50% of cases with 56E (N = 6/12) and in 40% of cases with 56A mismatch (N = 2/5). Correlation analysis between isolated HLA-DP DSA MFI and crossmatches (N = 90) showed negative crossmatch results with HLA-DP DSA MFI <2000 (N = 14). Below an MFI of 10,000 CDC crossmatches were also negative (N = 33). Above these MFI values both positive (N = 35) and negative (N = 16) crossmatch results were generated.

CONCLUSIONS:
Isolated HLA-DP DSA are rare, yet constitute a significant risk for AMR. We identified high-risk eplet mismatches that can lead to HLA-DP DSA formation. We therefore recommend HLA-DP typing to perform HLA-DP DSA analysis before transplantation. HLA-DP DSA with high MFI were not always correlated with positive crossmatch results.}},
  articleno    = {{101287}},
  author       = {{Daniëls, L and Claas, FHJ and Kramer, CSM and Senev, A and Vanden Driessche, M and Edmonds, MP and Van Laecke, Steven and Hellemans, R and Abramowicz, D and Naessens, M}},
  issn         = {{0966-3274}},
  journal      = {{TRANSPLANT IMMUNOLOGY}},
  keywords     = {{Crossmatch,Eplets.,HLA-DP antibodies,Human leukocyte antigen,Renal transplantation}},
  language     = {{eng}},
  pages        = {{9}},
  title        = {{The role of HLA-DP mismatches and donor specific HLA-DP antibodies in kidney transplantation : a case series}},
  url          = {{http://doi.org/10.1016/j.trim.2020.101287}},
  volume       = {{65}},
  year         = {{2021}},
}

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