The Influence of HLA-DP on Kidney Transplantation: A Systematic Review

The Influence of HLA-DP on Kidney Transplantation: A Systematic Review

Authors

  • Jocelito Pessotto Junior Universidade Federal de Santa Maria Author
  • Andrei Cezar Davis Universidade Federal de Ciências da Saúde de Porto Alegre Author
  • Arthur Felipe Kluge Universidade Federal de Ciências da Saúde de Porto Alegre Author
  • Igor Heineck Ouriques Universidade Federal de Ciências da Saúde de Porto Alegre Author
  • Mathias Parussolo Boniati Universidade Federal de Ciências da Saúde de Porto Alegre Author

DOI:

https://doi.org/10.51473/rcmos.v1i1.2026.1922

Keywords:

HLA-DP; Graft rejection; Donor-specific antibody; Crossmatch

Abstract

Kidney transplantation is the treatment of choice for end-stage renal disease, with HLA compatibility being a key determinant of graft outcomes. Although other HLA loci are routinely evaluated, the clinical impact of HLA-DP has not yet been fully elucidated. This systematic review aimed to assess the role of HLA-DP as a predictor of kidney transplant outcomes, including rejection, graft survival and loss, development of donor-specific antibodies (DSAs), and renal function. The review was conducted in accordance with PRISMA guidelines and included observational studies involving adult kidney transplant recipients that evaluated HLA-DP mismatches, DSA presence, expression levels, and clinical outcomes. Literature searches were performed in PubMed, Embase, and Lilacs databases, and methodological quality was assessed using the Newcastle–Ottawa Scale. Due to data heterogeneity, results were synthesized using a narrative approach. Seven studies were included. The presence of preformed anti–HLA-DP DSAs was independently associated with antibody-mediated acute rejection, with an impact comparable to that observed for HLA-DR and HLA-DQ. A higher burden of molecular incompatibilities was associated with poorer graft survival and accelerated decline in renal function, even in the presence of low-intensity antibodies. In conclusion, HLA-DP has significant clinical relevance in kidney transplant outcomes, underscoring the need for more detailed immunological assessment of this locus. 

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References

BAHIA. SECRETARIA DA SAÚDE. Processo de doação/transplantes. Salvador: SESAB, 2025.

BAXTER-LOWE, L. A. et al. Center-defined unacceptable HLA antigens facilitate transplants for sensitized patients in a multi-center kidney exchange program. American Journal of Transplantation, v. 14, n. 7, p. 1592-1598, 2014. DOI: https://doi.org/10.1111/ajt.12734

BRASIL. MINISTÉRIO DA SAÚDE. Lista de espera e transplantes realizados no Brasil no ano recorrente. Brasília, DF: MS, 2025.

BRASIL. MINISTÉRIO DA SAÚDE. Portaria de Consolidação nº 4, de 28 de setembro de 2017: consolida as normas sobre os sistemas e os subsistemas do Sistema Único de Saúde. Diário Oficial da União, Brasília, DF, 2017.

BRASIL. MINISTÉRIO DA SAÚDE. SECRETARIA DE ATENÇÃO ESPECIALIZADA À SAÚDE. Portaria nº 684, de 18 de junho de 2021: altera o Anexo XXII da Portaria de Consolidação nº 6/GM/MS, de 28 de setembro de 2017. Diário Oficial da União, Brasília, DF, 2021.

CHOO, S. Y. The HLA system: genetics, immunology, clinical testing, and clinical implications. Yonsei Medical Journal, v. 48, n. 1, p. 11-23, 2007. DOI: https://doi.org/10.3349/ymj.2007.48.1.11

DANIËLS, L. et al. The role of HLA-DP mismatches and donor specific HLA-DP antibodies in kidney transplantation: a case series. Transplant Immunology, v. 65, p. 101287, 2021. DOI: https://doi.org/10.1016/j.trim.2020.101287

DE MARCO, R. et al. HLA-DPB1 molecular mismatches are risk factors for acute rejection and low 5-year graft function in first kidney transplants. HLA, v. 101, n. 3, p. 228-238, 2023. DOI: https://doi.org/10.1111/tan.14911

DI COCCO, P. et al. Treatment strategies for antibody-mediated rejection in kidney transplantation and its prevention. OBM Transplantation, v. 4, n. 3, p. 1-16, 2020. DOI: https://doi.org/10.21926/obm.transplant.2003119

ERLICH, H. A.; OPELZ, G.; HANSEN, J. HLA DNA typing and transplantation. Immunity, v. 14, n. 4, p. 347-356, 2001. DOI: https://doi.org/10.1016/S1074-7613(01)00115-7

FRISCHKNECHT, L. et al. The impact of pre-transplant donor specific antibodies on the outcome of kidney transplantation: data from the Swiss transplant cohort study. Frontiers in Immunology, v. 13, p. 1005790, 2022. DOI: https://doi.org/10.3389/fimmu.2022.1005790

GARCÍA-JIMÉNEZ, S. et al. A personalised delisting strategy enables successful kidney transplantation in highly sensitised patients with preformed donor-specific anti-HLA antibodies. HLA, v. 103, n. 6, p. e15572, 2024. DOI: https://doi.org/10.1111/tan.15572

LABOUX, T. et al. Impact of preformed donor-specific anti-HLA-Cw and anti-HLA-DP antibodies on acute antibody-mediated rejection in kidney transplantation. Transplant International, v. 36, p. 11416, 2023. DOI: https://doi.org/10.3389/ti.2023.11416

LITMAN, G. W. Histocompatibility: colonial match and mismatch. Nature, v. 438, n. 7067, p. 437-439, 2005. DOI: https://doi.org/10.1038/438437a

LIWSKI, R. S.; GREENSHIELDS, A. L.; BRAY, R. A.; GEBEL, H. M. Becoming a chef in the human leukocyte antigen kitchen: interpretation and modification of human leukocyte antigen-antibody assays. Current Opinion in Organ Transplantation, v. 22, n. 4, p. 407-414, 2017. DOI: https://doi.org/10.1097/MOT.0000000000000423

METZGER, R. A. et al. Expanded criteria donors for kidney transplantation. American Journal of Transplantation, v. 3, supl. 4, p. 114-125, 2003. DOI: https://doi.org/10.1034/j.1600-6143.3.s4.11.x

PAGE, M. J. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ, v. 372, n. 71, 2021.

PAN, Q. et al. The impact of preformed and de novo HLA-DP antibodies in renal transplantation: a meta-analysis. HLA, v. 101, n. 2, p. 115-123, 2023. DOI: https://doi.org/10.1111/tan.14879

PATEL, R.; TERASAKI, P. I. Significance of the positive crossmatch test in kidney transplantation. New England Journal of Medicine, v. 280, n. 14, p. 735-739, 1969. DOI: https://doi.org/10.1056/NEJM196904032801401

ROCK, K. L.; REITS, E.; NEEFJES, J. Present yourself! By MHC class I and MHC class II molecules. Trends in Immunology, v. 37, n. 11, p. 724-737, 2016. DOI: https://doi.org/10.1016/j.it.2016.08.010

SCHIAVO, T. et al. The Halifax flow crossmatch protocol results according to the HLA class and MFI of the DSA. Brazilian Journal of Transplantation, v. 26, n. 1, p. e1223, 2023. DOI: https://doi.org/10.53855/bjt.v26i1.500_ENG

SEITZ, A. et al. Isolated pre-existing HLA-DP donor-specific antibodies are associated with poorer outcomes in renal transplantation. Kidney International Reports, v. 7, n. 10, p. 2251-2263, 2022. DOI: https://doi.org/10.1016/j.ekir.2022.07.014

SHIINA, T. et al. The HLA genomic loci map: expression, interaction, diversity and disease. Journal of Human Genetics, v. 54, n. 1, p. 15-39, 2009. DOI: https://doi.org/10.1038/jhg.2008.5

SIMON, A. K.; HOLLANDER, G. A.; MCMICHAEL, A. Evolution of the immune system in humans from infancy to old age. Proceedings of the Royal Society B: Biological Sciences, v. 282, n. 1821, p. 20143085, 2015. DOI: https://doi.org/10.1098/rspb.2014.3085

TANG, C. et al. Analysis of de novo donor-specific HLA-DPB1 antibodies in kidney transplantation. HLA, v. 98, n. 5, p. 423-430, 2021. DOI: https://doi.org/10.1111/tan.14422

WELLS, G. A. et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. [S. l.: s. n.], 2025.

Published

2026-01-12

How to Cite

PESSOTTO JUNIOR, Jocelito; DAVIS , Andrei Cezar; KLUGE , Arthur Felipe; HEINECK OURIQUES, Igor; PARUSSOLO BONIATI , Mathias. The Influence of HLA-DP on Kidney Transplantation: A Systematic Review: The Influence of HLA-DP on Kidney Transplantation: A Systematic Review. Multidisciplinary Scientific Journal The Knowledge, Brasil, v. 1, n. 1, 2026. DOI: 10.51473/rcmos.v1i1.2026.1922. Disponível em: https://submissoesrevistarcmos.com.br/rcmos/article/view/1922. Acesso em: 19 jan. 2026.