Variability of Immune Biomarkers with the Graft Function in Kidney Transplant Patients in India, an Observational Prospective Cohort Study

Bejugama Katyayani; Guditi Swarnalatha; Taduri Gangadhar

doi:doi:10.11648/j.iji.20231101.12

| Peer-Reviewed

Variability of Immune Biomarkers with the Graft Function in Kidney Transplant Patients in India, an Observational Prospective Cohort Study

Bejugama Katyayani, Guditi Swarnalatha, Taduri Gangadhar

Published in International Journal of Immunology (Volume 11, Issue 1)

Received: 31 July 2023 Accepted: 30 August 2023 Published: 14 September 2023

Views: Downloads:

Download PDF

Share This Article

Twitter
Linked In
Facebook

Abstract

In renal transplantation (RT), the major issue is to maintain the immune homeostasis, limiting graft rejection (GR), and promoting transplant tolerance. A total of 70 subjects of chronic kidney disease patients on maintenance haemodialysis, opted for RT and 20 controls were recruited. The Tregs% (CD4+CD25+), concentration of cytokines IL –10 and IL 17 were measured in pre-and post-transplant at a defined timelines with stable graft function (SGF) and with GR for two years, using flow cytometer and sandwich ELISA method. With SGF, Tregs% Baseline [8.5 (6.5–10.7) vs. HCs [14.25 (13–18), p < 0.01)], at Baseline vs. six months [11.54 (8.9–15)], p < 0.001); At Baseline [3.05 (1.05–5.2) vs. GR 8.5 (6.5–10.7), p < 0.05]. Serum IL 10 baseline [3.6 (2.56–4.6) vs. HC (6.4 (4.8-9.8), p<0.001]. Serum IL 17 levels at baseline [120 (92 - 176) vs. HC [20.88 (18-55), p<0.05], day four vs. baseline [180 (160.5-257.45); p<0.05], day 90 vs. baseline [53.3 (48-100), p< 0.05] and this was maintained for two years, with GR vs. baseline [190 (105-372); p<0.05]. ROC analysis of Tregs% (AUC of 0.758 and a p – value of <0.05), IL-10 (AUC of 0.8 and a p – value of 0.117), IL-17 (AUC of 0.937 and a p – value of <0.05). With SGF, Tregs % increased from 6 months, IL-17 decreased from 3 months, IL-10 did not show changes and continued till two years; with GR, Tregs% decreased from baseline, IL-10 did not show changes, and IL-17 increased due to high inflammation. ROC analysis showed that the Tregs% and IL-17 are better predictors of graft outcome. However, the association between biomarkers with graft function couldn’t be evaluated which needs further studies.

Published in	International Journal of Immunology (Volume 11, Issue 1)
DOI	10.11648/j.iji.20231101.12
Page(s)	6-12
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2023. Published by Science Publishing Group

Keywords

Renal Transplantation, Immune Biomarkers, Graft Function, Enzyme-linked Immunosorbent Assay, Flow Cytometer

References

[1]	Voora S, Adey DB. Management of Kidney Transplant Recipients by General Nephrologists: Core Curriculum 2019. Am J Kidney Dis. 2019 Jun; 73 (6): 866-879. doi: 10.1053/j.ajkd.2019.01.031. Epub 2019 Apr 11. PMID: 30981567.
[2]	Cooper JE. Evaluation and Treatment of Acute Rejection in Kidney Allografts. Clin J Am Soc Nephrol. 2020 Mar 6; 15 (3): 430-438. doi: 10.2215/CJN.11991019. Epub 2020 Feb 17. PMID: 32066593; PMCID: PMC7057293.
[3]	Ma L, Zhang H, Hu K, et al. The imbalance between Tregs, Th17 cells, and inflammatory cytokines among renal transplant recipients. BMC Immunol. 2015; 16: 56. Published 2015 Sep 23. Doi: 10.1186/s12865-015-0118-8.
[4]	Muckenhuber M, Wekerle T, Schwarz C. Costimulation blockade and Tregs in solid organ transplantation. Front Immunol. 2022 Sep 2; 13: 969633. doi: 10.3389/fimmu.2022.969633. PMID: 36119115; PMCID: PMC9478950.
[5]	Huang DL, He YR, Liu YJ, He HY, Gu ZY, Liu YM, Liu WJ, Luo Z, Ju MJ. The immunomodulation role of Th17 and Treg in renal transplantation. Front Immunol. 2023 Feb 1; 14: 1113560. doi: 10.3389/fimmu.2023.1113560. PMID: 36817486; PMCID: PMC9928745.
[6]	Juneja T, Kazmi M, Mellace M, Saidi RF. Utilization of Treg Cells in Solid Organ Transplantation. Front Immunol. 2022 Feb 4; 13: 746889. doi: 10.3389/fimmu.2022.746889. PMID: 35185868; PMCID: PMC8854209.
[7]	Nakagiri T, Inoue M, Minami M, Shintani Y, Okumura M. Immunology mini-review: the basics of T (H) 17 and interleukin-6 in transplantation. Transplant Proc. 2012 May; 44 (4): 1035-40. doi: 10.1016/j.transproceed.2011.12.032. PMID: 22564619.
[8]	San Segundo D, et al. Two-year follow-up of a prospective study of circulating regulatory T cells in renal transplant patients. Clin Transplant. 2010; 24, 386–393.
[9]	Mostafa G. Aly, Eman H. Ibrahim, Hristos Karakizlis, Rolf Weimer, Gerhard Opelz, Christian Morath, Martin Zeier, Naruemol Ekpoom and Volker Daniel. CD4+CD25+CD127-Foxp3+ and CD8+CD28- Tregs in Renal Transplant Recipients: Phenotypic Patterns, Association with Immunosuppressive Drugs, and Interaction with Effector CD8+ T Cells and CD19+IL-10+ Bregs. Front. Immunol., 15 July 2021; https://doi.org/10.3389/fimmu.2021.716559.
[10]	Presser D, Seste U et al. Differential kinetics of effector and regulatory T cells in patients on calcineurin inhibitor-based drug regimen. Kidney International (2009) 76, 557–569.
[11]	Krajewska M, Kościelska-Kasprzak K, Kamińska D, et al. Kidney Transplant Outcome Is Associated with Regulatory T Cell Population and Gene Expression Early after Transplantation. J Immunol Res. 2019; 7452019. doi: 10.1155/2019/7452019.
[12]	Chu Z-Q Q Ji. Sirolimus did not affect CD4 (+) CD25 (high) fork head box p3 (+) T cells of peripheral blood in renal transplant recipients. Transplant Proc. Jan-Feb 2013; 45 (1): 153-6.
[13]	Mederacke YS, Vondran FW, Kollrich S et al. Transient increase of activated regulatory T cells early after kidney transplantation Sci Rep. 2019 Jan 31; 9 (1): 1021.
[14]	Inomata T Jing Hua, Antonio Di Zazzo & Reza Dana. Impaired Function of Peripherally Induced Regulatory T Cells in Hosts at High Risk of Graft Rejection. Scientific Reports. 2016; volume 6, Article number: 39924.
[15]	Mirzakhani M, Shahbazi M, Akbari R, Oliaei F, Asgharpour M, Nikoueinejad H, Mohammadnia-Afrouzi M. Reduced CD4+ CD25++ CD45RA- Foxp3hi activated regulatory T cells and its association with acute rejection in patients with kidney transplantation. Transpl Immunol. 2020 Jun; 60: 101290.
[16]	Al-Wedaie F, Farid E, Tabbara K, El-Agroudy AE, Al-Ghareeb SM. T-regulatory cells in chronic rejection versus stable grafts. Exp Clin Transplant. 2015 Apr 13; 170-6. PMID: 25894149.
[17]	Sharad K Mittal, Raj Kumar Sharma, Amit Gupta, Sita Naik. Increased interleukin -10 production without expansion of CD4+CD25+ T-regulatory cells in early stable renal transplant patients’ calcineurin inhibitors. Clinical Trial. Transplantation. 2009 Aug 15; 88 (3): 435-41.
[18]	Morteza Bagheri, Ali Taghizadeh-Afshari, Saeed Abkhiz, Isa Abdi-Rad, Mohammadreza Mohammadi-Fallah, Mansour Alizadeh, Saeed Sadeghzadeh. Analysis of Interleukin-17 mRNA Level in the Urinary Cells of Kidney Transplant Recipients with Stable Function. Maedica (Bucur). 2017 Dec; 12 (4): 242-245.
[19]	Van Kooten C, Boonstra JG, Paape ME, et al. Interleukin-17 activates human renal epithelial cells in vitro and is expressed during renal allograft rejection. J Am Soc Nephrol. 1998; 9: 1526–1534.
[20]	Daniel V et al. Association of circulating interleukin (IL)-12- and IL-10- producing dendritic cells with time posttransplant, dose of immunosuppression, and plasma cytokines in renal-transplant recipients. Transplantation 2005; 79 (11): 1498–506.
[21]	Alwahaibi NY, Halima Khalfan Alissaei, Sara Abdullah Alshihi, Nadia Alabri, Samya Sulaiman Albalushi, Mohammed Albaloosh. Serum levels of TNF-α, IL-6 and IL-10 in hemodialysis and renal transplant patients and in healthy subjects. Port J Nephrol Hypert 2016; 30 (2): 194-198.

Cite This Article

Plain Text BibTeX RIS

APA Style

Bejugama Katyayani, Guditi Swarnalatha, Taduri Gangadhar. (2023). Variability of Immune Biomarkers with the Graft Function in Kidney Transplant Patients in India, an Observational Prospective Cohort Study. International Journal of Immunology, 11(1), 6-12. https://doi.org/10.11648/j.iji.20231101.12

Copy | Download

ACS Style

Bejugama Katyayani; Guditi Swarnalatha; Taduri Gangadhar. Variability of Immune Biomarkers with the Graft Function in Kidney Transplant Patients in India, an Observational Prospective Cohort Study. Int. J. Immunol. 2023, 11(1), 6-12. doi: 10.11648/j.iji.20231101.12

Copy | Download

AMA Style

Bejugama Katyayani, Guditi Swarnalatha, Taduri Gangadhar. Variability of Immune Biomarkers with the Graft Function in Kidney Transplant Patients in India, an Observational Prospective Cohort Study. Int J Immunol. 2023;11(1):6-12. doi: 10.11648/j.iji.20231101.12

Copy | Download

@article{10.11648/j.iji.20231101.12,
  author = {Bejugama Katyayani and Guditi Swarnalatha and Taduri Gangadhar},
  title = {Variability of Immune Biomarkers with the Graft Function in Kidney Transplant Patients in India, an Observational Prospective Cohort Study},
  journal = {International Journal of Immunology},
  volume = {11},
  number = {1},
  pages = {6-12},
  doi = {10.11648/j.iji.20231101.12},
  url = {https://doi.org/10.11648/j.iji.20231101.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.iji.20231101.12},
  abstract = {In renal transplantation (RT), the major issue is to maintain the immune homeostasis, limiting graft rejection (GR), and promoting transplant tolerance. A total of 70 subjects of chronic kidney disease patients on maintenance haemodialysis, opted for RT and 20 controls were recruited. The Tregs% (CD4+CD25+), concentration of cytokines IL –10 and IL 17 were measured in pre-and post-transplant at a defined timelines with stable graft function (SGF) and with GR for two years, using flow cytometer and sandwich ELISA method. With SGF, Tregs% Baseline [8.5 (6.5–10.7) vs. HCs [14.25 (13–18), p < 0.01)], at Baseline vs. six months [11.54 (8.9–15)], p < 0.001); At Baseline [3.05 (1.05–5.2) vs. GR 8.5 (6.5–10.7), p < 0.05]. Serum IL 10 baseline [3.6 (2.56–4.6) vs. HC (6.4 (4.8-9.8), p<0.001]. Serum IL 17 levels at baseline [120 (92 - 176) vs. HC [20.88 (18-55), p<0.05], day four vs. baseline [180 (160.5-257.45); p<0.05], day 90 vs. baseline [53.3 (48-100), p< 0.05] and this was maintained for two years, with GR vs. baseline [190 (105-372); p<0.05]. ROC analysis of Tregs% (AUC of 0.758 and a p – value of <0.05), IL-10 (AUC of 0.8 and a p – value of 0.117), IL-17 (AUC of 0.937 and a p – value of <0.05). With SGF, Tregs % increased from 6 months, IL-17 decreased from 3 months, IL-10 did not show changes and continued till two years; with GR, Tregs% decreased from baseline, IL-10 did not show changes, and IL-17 increased due to high inflammation. ROC analysis showed that the Tregs% and IL-17 are better predictors of graft outcome. However, the association between biomarkers with graft function couldn’t be evaluated which needs further studies.},
 year = {2023}
}

Copy | Download

TY  - JOUR
T1  - Variability of Immune Biomarkers with the Graft Function in Kidney Transplant Patients in India, an Observational Prospective Cohort Study
AU  - Bejugama Katyayani
AU  - Guditi Swarnalatha
AU  - Taduri Gangadhar
Y1  - 2023/09/14
PY  - 2023
N1  - https://doi.org/10.11648/j.iji.20231101.12
DO  - 10.11648/j.iji.20231101.12
T2  - International Journal of Immunology
JF  - International Journal of Immunology
JO  - International Journal of Immunology
SP  - 6
EP  - 12
PB  - Science Publishing Group
SN  - 2329-1753
UR  - https://doi.org/10.11648/j.iji.20231101.12
AB  - In renal transplantation (RT), the major issue is to maintain the immune homeostasis, limiting graft rejection (GR), and promoting transplant tolerance. A total of 70 subjects of chronic kidney disease patients on maintenance haemodialysis, opted for RT and 20 controls were recruited. The Tregs% (CD4+CD25+), concentration of cytokines IL –10 and IL 17 were measured in pre-and post-transplant at a defined timelines with stable graft function (SGF) and with GR for two years, using flow cytometer and sandwich ELISA method. With SGF, Tregs% Baseline [8.5 (6.5–10.7) vs. HCs [14.25 (13–18), p < 0.01)], at Baseline vs. six months [11.54 (8.9–15)], p < 0.001); At Baseline [3.05 (1.05–5.2) vs. GR 8.5 (6.5–10.7), p < 0.05]. Serum IL 10 baseline [3.6 (2.56–4.6) vs. HC (6.4 (4.8-9.8), p<0.001]. Serum IL 17 levels at baseline [120 (92 - 176) vs. HC [20.88 (18-55), p<0.05], day four vs. baseline [180 (160.5-257.45); p<0.05], day 90 vs. baseline [53.3 (48-100), p< 0.05] and this was maintained for two years, with GR vs. baseline [190 (105-372); p<0.05]. ROC analysis of Tregs% (AUC of 0.758 and a p – value of <0.05), IL-10 (AUC of 0.8 and a p – value of 0.117), IL-17 (AUC of 0.937 and a p – value of <0.05). With SGF, Tregs % increased from 6 months, IL-17 decreased from 3 months, IL-10 did not show changes and continued till two years; with GR, Tregs% decreased from baseline, IL-10 did not show changes, and IL-17 increased due to high inflammation. ROC analysis showed that the Tregs% and IL-17 are better predictors of graft outcome. However, the association between biomarkers with graft function couldn’t be evaluated which needs further studies.
VL  - 11
IS  - 1
ER  -

Copy | Download

Author Information

Bejugama Katyayani

Department of Microbiology, All India Institute of Medical Sciences, Bibinagar, India
Guditi Swarnalatha

Department of Nephrology, Nizams Institute of Medical Sciences, Hyderabad, India
Taduri Gangadhar

Department of Nephrology, Nizams Institute of Medical Sciences, Hyderabad, India

Download PDF

Sections

Plain Text BibTeX RIS

APA Style

Bejugama Katyayani, Guditi Swarnalatha, Taduri Gangadhar. (2023). Variability of Immune Biomarkers with the Graft Function in Kidney Transplant Patients in India, an Observational Prospective Cohort Study. International Journal of Immunology, 11(1), 6-12. https://doi.org/10.11648/j.iji.20231101.12

Copy | Download

ACS Style

Bejugama Katyayani; Guditi Swarnalatha; Taduri Gangadhar. Variability of Immune Biomarkers with the Graft Function in Kidney Transplant Patients in India, an Observational Prospective Cohort Study. Int. J. Immunol. 2023, 11(1), 6-12. doi: 10.11648/j.iji.20231101.12

Copy | Download

AMA Style

Bejugama Katyayani, Guditi Swarnalatha, Taduri Gangadhar. Variability of Immune Biomarkers with the Graft Function in Kidney Transplant Patients in India, an Observational Prospective Cohort Study. Int J Immunol. 2023;11(1):6-12. doi: 10.11648/j.iji.20231101.12

Copy | Download

@article{10.11648/j.iji.20231101.12,
  author = {Bejugama Katyayani and Guditi Swarnalatha and Taduri Gangadhar},
  title = {Variability of Immune Biomarkers with the Graft Function in Kidney Transplant Patients in India, an Observational Prospective Cohort Study},
  journal = {International Journal of Immunology},
  volume = {11},
  number = {1},
  pages = {6-12},
  doi = {10.11648/j.iji.20231101.12},
  url = {https://doi.org/10.11648/j.iji.20231101.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.iji.20231101.12},
  abstract = {In renal transplantation (RT), the major issue is to maintain the immune homeostasis, limiting graft rejection (GR), and promoting transplant tolerance. A total of 70 subjects of chronic kidney disease patients on maintenance haemodialysis, opted for RT and 20 controls were recruited. The Tregs% (CD4+CD25+), concentration of cytokines IL –10 and IL 17 were measured in pre-and post-transplant at a defined timelines with stable graft function (SGF) and with GR for two years, using flow cytometer and sandwich ELISA method. With SGF, Tregs% Baseline [8.5 (6.5–10.7) vs. HCs [14.25 (13–18), p < 0.01)], at Baseline vs. six months [11.54 (8.9–15)], p < 0.001); At Baseline [3.05 (1.05–5.2) vs. GR 8.5 (6.5–10.7), p < 0.05]. Serum IL 10 baseline [3.6 (2.56–4.6) vs. HC (6.4 (4.8-9.8), p<0.001]. Serum IL 17 levels at baseline [120 (92 - 176) vs. HC [20.88 (18-55), p<0.05], day four vs. baseline [180 (160.5-257.45); p<0.05], day 90 vs. baseline [53.3 (48-100), p< 0.05] and this was maintained for two years, with GR vs. baseline [190 (105-372); p<0.05]. ROC analysis of Tregs% (AUC of 0.758 and a p – value of <0.05), IL-10 (AUC of 0.8 and a p – value of 0.117), IL-17 (AUC of 0.937 and a p – value of <0.05). With SGF, Tregs % increased from 6 months, IL-17 decreased from 3 months, IL-10 did not show changes and continued till two years; with GR, Tregs% decreased from baseline, IL-10 did not show changes, and IL-17 increased due to high inflammation. ROC analysis showed that the Tregs% and IL-17 are better predictors of graft outcome. However, the association between biomarkers with graft function couldn’t be evaluated which needs further studies.},
 year = {2023}
}

Copy | Download

TY  - JOUR
T1  - Variability of Immune Biomarkers with the Graft Function in Kidney Transplant Patients in India, an Observational Prospective Cohort Study
AU  - Bejugama Katyayani
AU  - Guditi Swarnalatha
AU  - Taduri Gangadhar
Y1  - 2023/09/14
PY  - 2023
N1  - https://doi.org/10.11648/j.iji.20231101.12
DO  - 10.11648/j.iji.20231101.12
T2  - International Journal of Immunology
JF  - International Journal of Immunology
JO  - International Journal of Immunology
SP  - 6
EP  - 12
PB  - Science Publishing Group
SN  - 2329-1753
UR  - https://doi.org/10.11648/j.iji.20231101.12
AB  - In renal transplantation (RT), the major issue is to maintain the immune homeostasis, limiting graft rejection (GR), and promoting transplant tolerance. A total of 70 subjects of chronic kidney disease patients on maintenance haemodialysis, opted for RT and 20 controls were recruited. The Tregs% (CD4+CD25+), concentration of cytokines IL –10 and IL 17 were measured in pre-and post-transplant at a defined timelines with stable graft function (SGF) and with GR for two years, using flow cytometer and sandwich ELISA method. With SGF, Tregs% Baseline [8.5 (6.5–10.7) vs. HCs [14.25 (13–18), p < 0.01)], at Baseline vs. six months [11.54 (8.9–15)], p < 0.001); At Baseline [3.05 (1.05–5.2) vs. GR 8.5 (6.5–10.7), p < 0.05]. Serum IL 10 baseline [3.6 (2.56–4.6) vs. HC (6.4 (4.8-9.8), p<0.001]. Serum IL 17 levels at baseline [120 (92 - 176) vs. HC [20.88 (18-55), p<0.05], day four vs. baseline [180 (160.5-257.45); p<0.05], day 90 vs. baseline [53.3 (48-100), p< 0.05] and this was maintained for two years, with GR vs. baseline [190 (105-372); p<0.05]. ROC analysis of Tregs% (AUC of 0.758 and a p – value of <0.05), IL-10 (AUC of 0.8 and a p – value of 0.117), IL-17 (AUC of 0.937 and a p – value of <0.05). With SGF, Tregs % increased from 6 months, IL-17 decreased from 3 months, IL-10 did not show changes and continued till two years; with GR, Tregs% decreased from baseline, IL-10 did not show changes, and IL-17 increased due to high inflammation. ROC analysis showed that the Tregs% and IL-17 are better predictors of graft outcome. However, the association between biomarkers with graft function couldn’t be evaluated which needs further studies.
VL  - 11
IS  - 1
ER  -

Copy | Download