Increased Proportion of Circulating T Follicular Helper Cells and Serum Levels of IL-21 in Antibody-Mediated Rejection of Renal Allograft
DOI:
https://doi.org/10.61186/Keywords:
Kidney transplant, Antibody-mediated rejection, T follicular helper cell, Interleukin-21Abstract
Introduction. Antibody-mediated rejection (AMR) is one of the major obstacles to successful kidney transplantation. The T helper cell subset that plays a key role in the activation of B-lymphocytes and antibody production is T follicular helper (Tfh) cell. Therefore, we aimed to compare the percentage of Tfh cells and the serum level of interleukin 21 (IL-21), mainly secreted by this subset, in patients with AMR and stable recipients.
Methods. Peripheral blood samples were taken from 30 patients diagnosed with AMR and 30 stable kidney transplant recipients as well as 10 age- and sex-matched healthy individuals. The percentage of circulating Tfh cells (TCD4+CXCR5+PD1+) and the level of IL-21 were studied by flow cytometry and ELISA techniques, respectively.
Results. The proportion of cTfh cells among circulating TCD4+ cells in AMR patients was markedly elevated compared to the other groups (P < .0001). It was also higher in stable recipients than in healthy controls (P < .0001). The serum level of IL-21 was increased in AMR patients compared to stable recipients (P = .03) and healthy participants (P = .02). In addition, there was a significant negative correlation between cTfh percentage and the estimated glomerular filtration rate (eGFR) in transplanted patients (P = .001). Moreover, the AUC of cTfh cells in AMR diagnosis was 0.83 [95% CI 0.73-0.93 (P < .0001)].
Conclusion. In AMR patients, cTfh cell percentage and IL-21 levels were significantly increased. The significant association between cTfh % and eGFR, with an AUC of 0.83, indicates its potential as a diagnostic and prognostic marker in AMR.
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References
1. Garces JC, Giusti S, Staffeld-Coit C, Bohorquez H, Cohen AJ, Loss GEJOJ. Antibody-mediated rejection: a review. 2017;17(1):46-55.
2. Petersone L, Walker LSJII. T-cell help in the germinal center: homing in on the role of IL-21. 2024;36(3):89-98.
3. Crotty SJI. T follicular helper cell biology: a decade of discovery and diseases. 2019;50(5):1132-48.
4. Chong AS. Mechanisms of organ transplant injury mediated by B cells and antibodies: Implications for antibody-mediated rejection. American Journal of Transplantation. 2020;20:23-32.
5. Leonard WJ, Wan C-KJF. IL-21 signaling in immunity. 2016;5.
6. Spolski R, Leonard WJJIi. IL-21 and T follicular helper cells. 2010;22(1):7-12.
7. Xie A, Buras ED, Xia J, Chen WJJoc, immunology c. The emerging role of interleukin-21 in transplantation. 2012(2):1.
8. Désy O, Béland S, Thivierge M-P, Marcoux M, Desgagnés
J- S, Bouchard-Boivin F, et al. T follicular helper cells expansion in transplant recipients correlates with graft infiltration and adverse outcomes. 2024;15:1275933.
9. Liu J, Tang T, Qu Z, Wang L, Si R, Wang H, et al. Elevated number of IL-21+ TFH and CD86+ CD38+ B cells in blood of renal transplant recipients with AMR under conventional immuno-suppression. 2022;36:20587384211048027.
10. Mendoza Rojas A, van Gelder T, de Kuiper R, Reijerkerk D, Clahsen-van Groningen MC, Hesselink DA, et al. Pre-transplant donor-reactive IL-21 producing T cells as a tool to identify an increased risk for acute rejection. 2021;11(1):12445.
11. Liu J, Yue W-L, Fan H-Z, Luo Y-S, Feng G-W, Li J-FJTI. Correlation of cTfh cells and memory B cells with AMR after renal transplantation. 2024;86:102095.
12. Walters GD, Vinuesa CGJT. T follicular helper cells in transplantation. 2016;100(8):1650-5.
13. Loupy A, Haas M, Roufosse C, Naesens M, Adam B, Afrouzian M, et al. The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell–and antibody-mediated rejection. Wiley Online Library; 2020.
14. Davis S, Cooper JEJTr. Acute antibody-mediated rejection in kidney transplant recipients. 2017;31(1):47-54.
15. Ueno HJJoci. Human circulating T follicular helper cell subsets in health and disease. 2016;36:34-9.
16. Louis K, Macedo C, Bailly E, Lau L, Ramaswami B, Marrari M, et al. Coordinated circulating T follicular helper and activated B cell responses underlie the onset of antibody-mediated rejection in kidney transplantation. 2020;31(10):2457-74.
17. Chen W, Bai J, Huang H, Bi L, Kong X, Gao Y, et al. Low proportion of follicular regulatory T cell in renal transplant patients with chronic antibody-mediated rejection.
2017;7(1):1322.
18. Macedo C, Hadi K, Walters J, Elinoff B, Marrari M, Zeevi A, et al. Impact of induction therapy on circulating T follicular helper cells and subsequent donor-specific antibody formation after kidney transplant. 2019;4(3):455-69.
19. Yan L, Li Y, Li Y, Wu X, Wang X, Wang L, et al. Increased circulating Tfh to Tfr ratio in chronic renal allograft dysfunction: a pilot study. 2019;20:1-11.
20. Shi J, Luo F, Shi Q, Xu X, He X, Xia YJBn. Increased circulating follicular helper T cells with decreased programmed death-1 in chronic renal allograft rejection. 2015;16:1-6.
21. Choi J, Crotty S, Choi YSJIN. Cytokines in follicular helper T cell biology in physiologic and pathologic conditions. 2024;24(1).
22. Li YM, Li Y, Shi YY, Yan L, Wu XJ, Tang JT, et al. Impact of immunosuppressive drugs on circulating Tfh cells in kidney transplant recipients: a pilot study. 2018;46:1-7.
23. Ma N, Wu W-B, Zhao X-Y, Xu L-P, Zhang X-H, Wang
Y, et al. Targeting TFH cells is a novel approach for donor-specific antibody desensitization of allograft candidates: an in vitro and in vivo study. Haematologica. 2024;109(4):1233.
