• P-ISSN 0974-6846 E-ISSN 0974-5645

Indian Journal of Science and Technology


Indian Journal of Science and Technology

Year: 2023, Volume: 16, Issue: 7, Pages: 509-515

Original Article

Assessment of Cytokines as Potential Biomarkers to Predict Allograft Rejection in Kidney Transplant Recipients

Received Date:06 December 2022, Accepted Date:24 January 2023, Published Date:23 February 2023


Objectives: Allograft rejection is the most common event that occurs posttransplant and the current diagnostic tools like the measurement of serum creatinine or core kidney biopsy could not serve as a predictive tool and have certain drawbacks. Thus, our target was to find potential, non-invasive, and predictive biomarkers which could identify recipients at the risk of post-transplant allograft rejection. Methods: It is a prospective longitudinal cohort study comprising of 40 live-related kidney transplant recipients whose peripheral blood was collected at three time points viz pre, one and threemonths post-transplant to assess the plasma cytokine levels of FOXP3, IL- 6, IL-17 and TGF-b using Enzyme linked immunosorbent assay (ELISA). The patients were clinically followed for period of two years to determine their posttransplant outcome. Findings: 13 of our recipients had biopsy proven allograft rejection at the end of follow-up period. The pre-transplant concentration of FOXP3 were less in the rejection group whereas the concentration of IL-6, IL- 17 and TGF- b were more in the rejection group (p<0.05). The classification accuracy of the markers FOXP3, TGF- b , IL-17 and IL-6 were assessed and they had an AUC of 1.0, 1.0, 0.96 and 0.84 respectively with high sensitivity, specificity, and statistical significance. Novelty: Pre-transplant levels of plasma cytokines were able to predict recipients at the risk of allograft rejection. Thus, our study confirms the predictive power of our cytokine biomarkers FOXP3, IL- 6, IL-17 and TGF-b and further paves way for personalized immunosuppressive regimen.

Keywords: Predictive Biomarkers; Allograft Rejection; FOXP3; IL6; IL17; TGFb


  1. Swanson KJ, Aziz F, Garg N, Mohamed M, Mandelbrot D, Djamali A, et al. Role of novel biomarkers in kidney transplantation. World Journal of Transplantation. 2020;10(9):230–255. Available from: https://doi.org/10.5500/wjt.v10.i9.230
  2. Lim JHH, Chung BH, Lee SHH, Jung HYY, Choi JYY, Cho JHH, et al. Omics-based biomarkers for diagnosis and prediction of kidney allograft rejection. The Korean Journal of Internal Medicine. 2022;37(3):520–533. Available from: https://doi.org/10.3904/kjim.2021.518
  3. Georgiev P, Charbonnier LMM, Chatila TA. Regulatory T Cells: the Many Faces of Foxp3. Journal of Clinical Immunology. 2019;39(7):623–640. Available from: https://doi.org/10.1007/s10875-019-00684-7
  4. Bent EH, Millán-Barea LR, Zhuang I, Goulet DR, Fröse J, Hemann MT. Microenvironmental IL-6 inhibits anti-cancer immune responses generated by cytotoxic chemotherapy. Nature Communications. 2021;12(1):1–13. Available from: https://doi.org/10.1038/s41467-021-26407-4
  5. Biswas PS. IL-17 in Renal Immunity and Autoimmunity. The Journal of Immunology. 2018;201(11):3153–3159. Available from: https://doi.org/10.4049/jimmunol.1801042
  6. Wang J, Xu Z, Wang Z, Du G, Lun L. TGF-beta signaling in cancer radiotherapy. Cytokine. 2021;148:155709. Available from: https://doi.org/10.1016/j.cyto.2021.155753
  7. Hart A, Singh D, Brown SJ, Wang JH, Kasiske BL. Incidence, risk factors, treatment, and consequences of antibody‐mediated kidney transplant rejection: A systematic review. Clinical Transplantation. 2021;35(7). Available from: https://doi.org/10.1111/ctr.14320
  8. Lee J, Kim EJ, Lee JG, Kim BS, Huh KH, Kim MS, et al. Clinical impact of serum bilirubin levels on kidney transplant outcomes. Scientific Reports. 2021;11(1):6889. Available from: https://doi.org/10.1038/s41598-021-86330-y
  9. Ito A, Sugimura J, Matsuura T, Abe T, Obara W. Plasma cytokine levels before and 1 year after successful living-donor renal transplantation. Renal Replacement Therapy. 2020;6(1):1–9. Available from: https://doi.org/10.1186/s41100-020-00298-5
  10. Torabijahromi M, Roozbeh J, Raeesjalali G, Shafiee M, Rasaei N, Heidari M, et al. Comparison of FOXP3 and Interleukin 35 Expression Profiles in Kidney Transplant Recipients With Excellent Long-Term Graft Function and Acute Rejection. Experimental and Clinical Transplantation. 2021;19(11):1142–1148. Available from: https://doi.org/10.6002/ect.2021.0116
  11. Salehi S, Shahi A, Afzali S, Keshtkar AA, Bonab SF, Soleymanian T, et al. Transitional immature regulatory B cells and regulatory cytokines can discriminate chronic antibody-mediated rejection from stable graft function. International Immunopharmacology. 2020;86:106750. Available from: https://doi.org/10.1016/j.intimp.2020.106750
  12. Doberer K, Duerr M, Halloran PF, Eskandary F, Budde K, Regele H, et al. A Randomized Clinical Trial of Anti–IL-6 Antibody Clazakizumab in Late Antibody-Mediated Kidney Transplant Rejection. Journal of the American Society of Nephrology. 2021;32(3):708–722. Available from: https://doi.org/10.1681/ASN.2020071106
  13. Wang Y, Hang G, Wen Q, Wang H, Bao L, Chen B. Changes and Significance of IL-17 in Acute Renal Allograft Rejection in Rats. Transplantation Proceedings. 2022;54(7):2021–2024. Available from: https://doi.org/10.1016/j.transproceed.2022.05.019


© 2023 Priscilla et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Published By Indian Society for Education and Environment (iSee)


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