Impact of CD 28, CD86, CTLA-4 and PD-1 genes polymorphisms on acute renal allograft rejection and graft survival among Egyptian recipients.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
24 Jan 2024
Historique:
received: 24 06 2023
accepted: 15 01 2024
medline: 25 1 2024
pubmed: 25 1 2024
entrez: 24 1 2024
Statut: epublish

Résumé

To study the impact of four gene polymorphisms on acute renal allograft rejection (AR) and graft survival among Egyptian population. These 4 gene polymorphisms include: (1) CD 28 (rs3116496), (2) CD86 (rs1129055), (3) CTLA-4 (rs3087243), (4) PD-1 (rs2227982). This is a non-concurrent cohort study including 50 kidney transplant recipients diagnosed histopathologically as (AR) [study group] and another 50 matched allograft recipients without AR [control group]. Blood samples were taken from both groups and subjected to genotyping for the selected four genetic polymorphisms by TaqMan genotyping assay. The difference in genotypic distribution of CD 28: rs3116496 and CD86: rs1129055 wasn't statistically significant between the study and control groups (P = 0.22 and 0.33 respectively) and also both polymorphisms had no effect on graft survival (P = 0.36 and 0.74 respectively) while the addition of C allele to IVS3 +17T/C polymorphism in CD28 gene showed a protective effect against AR (P = 0.03). CTLA-4: rs3087243 AG genotype showed a protective effect against AR as it was more frequent in no rejection group compared to those with AR (P = 0.001) with a statistically significant impact on graft survival (P < 0.001), while PD-1: rs2227982 AG genotype was equally distributed between both groups (variant of unknown significance). There was no detected association between CD86 polymorphism: rs1129055 and CD 28 polymorphism: rs3116496 with the development of AR. However, C allele of CD 28 IVS3 +17T/C polymorphism and CTLA-4 polymorphism: rs3087243AG genotype both demonstrated a protective effect against AR.

Identifiants

pubmed: 38267522
doi: 10.1038/s41598-024-52195-0
pii: 10.1038/s41598-024-52195-0
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2047

Subventions

Organisme : Science, Technology, and Innovation Funding Authority in Egypt (STDF)
ID : (Grant No 26300).

Informations de copyright

© 2024. The Author(s).

Références

Lim, W. H. et al. Human leukocyte antigen mismatches associated with increased risk of rejection, graft failure, and death independent of initial immunosuppression in renal transplant recipients. Clin. Transplant. 26(4), E428–E437 (2012).
doi: 10.1111/j.1399-0012.2012.01654.x pubmed: 22672477
Siu, J. H. Y., Surendrakumar, V., Richards, J. A. & Pettigrew, G. J. T cell allorecognition pathways in solid organ transplantation. Front. Immunol. 5(9), 2548 (2018).
doi: 10.3389/fimmu.2018.02548
Habicht, A. & Sayegh, M. H. T cell costimulatory pathways in allograft rejection and tolerance: What’s new?. Curr. Opin. Organ. Transplant. 12(1), 17–22 (2007).
doi: 10.1097/MOT.0b013e328012b651 pubmed: 27792084
Han, F. F. et al. Association between co-stimulatory molecule gene polymorphism and acute rejection of allograft. Transpl. Immunol. 31(2), 81–86 (2014).
doi: 10.1016/j.trim.2014.06.003 pubmed: 24952299
Pawlik, A., Dabrowska-Zamojcin, E., Dziedziejko, V., Safranow, K. & Domanski, L. Association between IVS3 +17T/C CD28 gene polymorphism and the acute kidney allograft rejection. Transpl. Immunol. 30(2–3), 84–87 (2014).
doi: 10.1016/j.trim.2013.12.002 pubmed: 24368148
Kusztal, M. et al. The influence of CTLA-4 gene polymorphism on long-term kidney allograft function in Caucasian recipients. Transpl. Immunol. 23(3), 121–124 (2010).
doi: 10.1016/j.trim.2010.05.002 pubmed: 20470888
Geng, P. et al. Distinct role of CD86 polymorphisms (rs1129055, rs17281995) in risk of cancer: Evidence from a meta-analysis. PLoS ONE. 9(11), e109131 (2014).
doi: 10.1371/journal.pone.0109131 pubmed: 25369324 pmcid: 4219668
Matsushita, M., Tsuchiya, N., Oka, T., Yamane, A. & Tokunaga, K. New polymorphisms of human CD80 and CD86: Lack of association with rheumatoid arthritis and systemic lupus erythematosus. Genes Immun. 1(7), 428–434 (2000).
doi: 10.1038/sj.gene.6363704 pubmed: 11196673
Choi, J., Bano, A. & Azzi, J. Biomarkers in solid organ transplantation. Clin. Lab. Med. 39(1), 73–85 (2019).
doi: 10.1016/j.cll.2018.11.003 pubmed: 30709510
Krichen, H. et al. CD86 +1057G>A polymorphism and susceptibility to acute kidney allograft rejection. Iran J. Kidney Dis. 5(3), 187–193 (2011).
pubmed: 21525579
Haas, M. et al. The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials. Am. J. Transplant. 18(2), 293–307 (2018).
doi: 10.1111/ajt.14625 pubmed: 29243394 pmcid: 5817248
Howard, T. D. et al. Fine mapping of an IgE-controlling gene on chromosome 2q: Analysis of CTLA4 and CD28. J. Allergy Clin. Immunol. 110(5), 743–751 (2002).
doi: 10.1067/mai.2002.128723 pubmed: 12417883
Kittai, A. S., Oldham, H., Cetnar, J. & Taylor, M. Immune checkpoint inhibitors in organ transplant patients. J. Immunother. 40(7), 277–281 (2017).
doi: 10.1097/CJI.0000000000000180 pubmed: 28719552
Domański, L. et al. The impact of rs231775 (+49AG) CTLA4 gene polymorphism on transplanted kidney function. Ann. Transplant. 17(3), 29–35 (2012).
doi: 10.12659/AOT.883455 pubmed: 23018253
Slavcheva, E. et al. Cytotoxic T-lymphocyte antigen 4 gene polymorphisms and susceptibility to acute allograft rejection. Transplantation. 72(5), 935–940 (2001).
doi: 10.1097/00007890-200109150-00032 pubmed: 11571462
Ono, K. et al. Polymorphisms in CTLA-4 predict de novo donor specific antibody formation after kidney transplantation. Hum. Immunol. 83(6), 494–498 (2022).
doi: 10.1016/j.humimm.2022.03.008 pubmed: 35365357
Dmitrienko, S., Hoar, D. I., Balshaw, R. & Keown, P. A. Immune response gene polymorphisms in renal transplant recipients. Transplantation. 80(12), 1773–1782 (2005).
doi: 10.1097/01.tp.0000184624.54005.9f pubmed: 16378074
Haimila, K. et al. Association of genetic variation in inducible costimulator gene with outcome of kidney transplantation. Transplantation. 87(3), 393–396 (2009).
doi: 10.1097/TP.0b013e318192897a pubmed: 19202444
Prokunina, L. et al. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat. Genet. 32(4), 666–669 (2002).
doi: 10.1038/ng1020 pubmed: 12402038
Kittles, R. A. & Weiss, K. M. Race, ancestry, and genes: Implications for defining disease risk. Annu. Rev. Genomics Hum. Genet. 4, 33–67 (2003).
doi: 10.1146/annurev.genom.4.070802.110356 pubmed: 14527296
Gendzekhadze, K., Rivas-Vetencourt, P. & Montano, R. F. Risk of adverse post-transplant events after kidney allograft transplantation as predicted by CTLA-4 +49 and TNF-alpha -308 single nucleotide polymorphisms: A preliminary study. Transpl. Immunol. 16(3–4), 194–199 (2006).
doi: 10.1016/j.trim.2006.09.001 pubmed: 17138053
Santiago, J. L. et al. Association of polymorphisms in T-cell activation costimulatory/inhibitory signal genes with allograft kidney rejection risk. Front. Immunol. 2(12), 650979 (2021).
doi: 10.3389/fimmu.2021.650979
Shokeir, A. A. et al. Egyptian clinical practice guideline for kidney transplantation. Arab. J. Urol. 19(2), 105–122 (2021).
doi: 10.1080/2090598X.2020.1868657 pubmed: 34104484 pmcid: 8158205
Guo, Y. F., Qiu, J. X., Guo, F., Liu, Y. & Shang, M. H. CTLA4 polymorphisms and de novo malignancy risk after renal transplantation in Chinese recipients. BioMed Res. Int. 2015, 986780 (2015).
doi: 10.1155/2015/986780 pubmed: 25667935 pmcid: 4312582
Liu, K. et al. Impact of inducible co-stimulator gene polymorphisms on acute rejection in renal transplant recipients: An updated systematic review and meta-analysis. Meta Gene 12, 118–124 (2017).
doi: 10.1016/j.mgene.2017.03.002
Marín, L. A. et al. Evaluation of CD86 gene polymorphism at +1057 position in liver transplant recipients. Transpl. Immunol. 15(1), 69–74 (2005).
doi: 10.1016/j.trim.2005.04.003 pubmed: 16223675
Canossi, A. et al. Influence of cytotoxic T-lymphocyte antigen-4 polymorphisms on acute rejection onset of cadaveric renal transplants. Transplant. Proc. 45(7), 2645–2649 (2013).
doi: 10.1016/j.transproceed.2013.07.008 pubmed: 24034013
Gao, J. W. et al. Polymorphisms in cytotoxic T lymphocyte associated antigen-4 influence the rate of acute rejection after renal transplantation in 167 Chinese recipients. Transpl. Immunol. 26(4), 207–211 (2012).
doi: 10.1016/j.trim.2012.02.005 pubmed: 22418270
Ruhi, Ç. et al. The influence of CTLA-4 single nucleotide polymorphisms on acute kidney allograft rejection in Turkish patients. Clin. Transplant. 29(7), 612–618 (2015).
doi: 10.1111/ctr.12563 pubmed: 25981560
Zolfaghari, L. et al. Association of programmed cell death 1 and programmed cell death 1 ligand gene polymorphisms with delayed graft function and acute rejection in kidney allograft recipients. Iran J. Kidney Dis. 9(2), 138–145 (2015).
pubmed: 25851293

Auteurs

Moatasem Elsayed Ghoneim (ME)

Nephrology and Transplant Unit, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt. moatasemelsayed@windowslive.com.

Hussein Sheashaa (H)

Nephrology and Transplant Unit, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.

Ehab Wafa (E)

Nephrology and Transplant Unit, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.

Amira Awadalla (A)

Center of Excellence for Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.

Asmaa E Ahmed (AE)

Genetics Research Unit, Faculty of Medicine, Delta University for Science and Technology, Gamasa, Egypt.

Mohamed Sobh (M)

Nephrology and Transplant Unit, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.

Ahmed Abdulrahman Shokeir (AA)

Department of Urology, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
Center of Excellence for Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.

Classifications MeSH