Frequency of Th1 and Th17 Cells and IL‐17A Levels in Peripheral Blood and Peritoneal Effluent in a Cohort of Patients Undergoing Peritoneal Dialysis: A Cross‐Sectional Study
DOI:
https://doi.org/10.71749/pkj.40Keywords:
Peritoneal Dialysis, Th1 cells, Th17 cells, Interleukin-17, Renal Insufficiency, ChronicAbstract
Introduction: Chronic kidney disease is characterized by an immune imbalance. In peritoneal dialysis (PD), chronic expo‐ sure to high‐load glucose solutions may further aggravate such disturbances. Among these inflammatory mediators, T helper 1 (Th1) and Th17 cells as well as interleukin 17A (IL‐17A) seem to stand out. We aimed to quantify the frequency of Th1 and Th17 cell subsets and IL‐17A levels in blood and peritoneal effluent (PE), looking at the peritoneal membrane (PM) and PD prescription characteristics as potential immune modulators.Methods: Cross‐sectional study of 26 PD patients and 10 healthy, age and sex‐matched controls. Cell frequencies were determined by flow cytometry and IL‐17A concentration was measured by enzyme‐linked immunosorbent assay. PD patients were evaluated according to PD prescription and PM characteristics.
Results: Blood Th1 cells’ frequency was decreased in PD patients (p=0.001) and icodextrin users had a lower frequency of Th17 cells, when compared to healthy controls (p=0.030). The immune cell profile of PE mimicked that of blood, except for Th1 cells, whose frequency was higher in PE (p<0.001). IL‐17A concentration was higher in PE (p=0.039), without a concomitant increase in Th17 cells. In subgroup analysis, increased IL‐17A was documented in PE of patients in automated PD (p=0.028) and those without a previous history of peritonitis (p=0.022).
Conclusion: Long‐term PD seems to modify both circulating and peritoneal immune cell profiles. The distribution of immune cells in PE closely mirrored that of blood, except for Th1 cells. Increased IL‐17A levels in PE may explain the deleterious long‐term effects of PD in the PM.
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References
Hill, N. et al. Global Prevalence of Chronic Kidney Disease – A Systematic Review and Meta-Analysis. PLoS One 11, e0158765 (2016).
Ammirati, A. Chronic Kidney Disease. Rev Assoc Med Bras 66, s03–s09 (2020).
Murton, M. et al. Burden of Chronic Kidney Disease by KDIGO Categories of Glomerular Filtration Rate and Albuminuria: A Systematic Review. Adv Ther 38, 180–200 (2021).
Perlman, R. L. & Heung, M. Renal Disease. in Pathophysiology of Disease: An Introduction to Clinical Medicine (ed. Hammer GD and McPhee SJ) (McGraw Hill, 2019).
Kato, S. et al. Aspects of Immune Dysfunction in End-stage Renal Disease. Clinical Journal of the American Society of Nephrology 3, 1526–1533 (2008).
Cho, Y. et al. Peritoneal Dialysis Use and Practice Patterns: An International Survey Study. American Journal of Kidney Diseases 77, 315–325 (2021).
Devuyst, O., Topley, N. & Williams, J. Morphological and functional changes in the dialysed peritoneal cavity: impact of more biocompatible solutions. Nephrology Dialysis Transplantation 17, 12–15 (2002).
Williams, J. et al. Morphologic Changes in the Peritoneal Membrane of Patients with Renal Disease. Journal of the American Society of Nephrology 13, 470–479 (2002).
Bartosova, M. & Schmitt, C. Biocompatible Peritoneal Dialysis: The Target Is Still Way Off. Front Physiol 9, (2018).
Salzer, W. Peritoneal dialysis-related peritonitis: challenges and solutions. Int J Nephrol Renovasc Dis 11, 173–186 (2018).
Peritoneal Dialysis Adequacy Work Group. Clinical Practice Guidelines for Peritoneal Dialysis Adequacy. American Journal of Kidney Diseases 48, S98–S129 (2006).
Gangji, A., Brimble, K. & Margetts, P. Association between Markers of Inflammation, Fibrosis and Hypervolemia in Peritoneal Dialysis Patients. Blood Purif 28, 354–358 (2009).
Baroni, G., Schuinski, A., de Moraes, T., Meyer, F. & Pecoits-Filho, R. Inflammation and the Peritoneal Membrane: Causes and Impact on Structure and Function during Peritoneal Dialysis. Mediators Inflamm 2012, (2012).
Zhou, Q., Bajo, M., del Peso, G., Yu, X. & Selgas, R. Preventing peritoneal membrane fibrosis in peritoneal dialysis patients. Kidney Int 90, 515–524 (2016).
Rodrigues-Díez, R. et al. IL-17A is a novel player in dialysis-induced peritoneal damage. Kidney Int 86, 303–315 (2014).
Vila Cuenca, M. et al. Differences in peritoneal response after exposure to low-GDP bicarbonate/lactate-buffered dialysis solution compared to conventional dialysis solution in a uremic mouse model. Int Urol Nephrol 50, 1151–1161 (2018).
Liappas, G. et al. Immune-Regulatory Molecule CD69 Controls Peritoneal Fibrosis. Journal of the American Society of Nephrology 27, 3561–3576 (2016).
Marchant, V. et al. IL-17A as a Potential Therapeutic Target for Patients on Peritoneal Dialysis. Biomolecules 10, 1361 (2020).
Witowski, J., Kamhieh-Milz, J., Kawka, E., Catar, R. & Jörres, A. IL-17 in Peritoneal Dialysis-Associated Inflammation and Angiogenesis: Conclusions and Perspectives. Front Physiol 9, 1694 (2018).
Ramani, K. et al. Disruption of interleukin-17 receptor A (IL-17RA) gene in mice aggravates renal interstitial fibrosis in obstructive nephropathy. Journal of Immunology 196, (2016).
Zamauskaite, A., Yaqoob, M., Madrigal, J. & Cohen, S. The frequency of Th2 type cells increases with time on peritoneal dialysis in patients with diabetic nephropathy. Eur Cytokine Netw 10, 219–226 (1999).
Yoh K, Ojima M, Takahashi S. Th2-biased GATA-3 transgenic mice developed severe experimental peritoneal fibrosis compared with Th1-biased T-bet and Th17-biased RORγt transgenic mice. Exp Anim. 2015;64(4):353–62.
Twardowski ZJ. The Fast Peritoneal Equilibration Test. Semin Dial. 2007 Oct 1;3(3):141–2.
Mousset, C. et al. Comprehensive Phenotyping of T Cells Using Flow Cytometry. Cytometry Part A 95, 647–654 (2019).
Littman DR, Rudensky AY. Th17 and Regulatory T Cells in Mediating and Restraining Inflammation. Cell. 2010 Mar;140(6):845–58.
Zhu, X. et al. Correlation of increased Th17/Treg cell ratio with endoplasmic reticulum stress in chronic kidney disease. Medicine 97, e10748 (2018).
Ma, L. et al. The imbalance between Tregs, Th17 cells and inflammatory cytokines among renal transplant recipients. BMC Immunol 16, 56 (2015).
Patel, D. & Kuchroo, V. Th17 Cell Pathway in Human Immunity: Lessons from Genetics and Therapeutic Interventions. Immunity 43, 1040–51 (2015).
Turner, J., Paust, H., Steinmetz, O. & Panzer, U. The Th17 immune response in renal inflammation. Kidney Int 77, 1070–5 (2010).
Basile, D., Ullah, M., Collet, J. & Mehrotra, P. T helper 17 cells in the pathophysiology of acute and chronic kidney disease. Kidney Res Clin Pract 40, 12–28 (2021).
Paust, H. et al. The IL-23/Th17 axis contributes to renal injury in experimental glomerulonephritis. Journal of the American Society of Nephrology 20, 969–79 (2009).
Orejudo, M. et al. Interleukin 17A Participates in Renal Inflammation Associated to Experimental and Human Hypertension. Front Pharmacol 10, 1015 (2019).
Mistry CD, Gokal R, Peers E, Brown CB, Smith S, Edwards DL, et al. A randomized multicenter clinical trial comparing isosmolar Icodextrin with hyperosmolar glucose solutions in CAPD. Kidney Int. 1994 Aug;46(2):496–503.
Szeto CC, Johnson DW. Low GDP Solution and Glucose-Sparing Strategies for Peritoneal Dialysis. Semin Nephrol. 2017 Jan;37(1):30–42.
Madhur MS, Lob HE, McCann LA, Iwakura Y, Blinder Y, Guzik TJ, et al. Interleukin 17 Promotes Angiotensin II–Induced Hypertension and Vascular Dysfunction. Hypertension. 2010 Feb;55(2):500–7.
Cornelius DC, Hogg JP, Scott J, Wallace K, Herse F, Moseley J, et al. Administration of Interleukin-17 Soluble Receptor C Suppresses T H 17 Cells, Oxidative Stress, and Hypertension in Response to Placental Ischemia During Pregnancy. Hypertension. 2013 Dec;62(6):1068–73.
Libetta, C. et al. Effects of different peritoneal dialysis fluids on the TH1/TH2 balance. Eur Cytokine Netw 22, 24–31 (2011).
Lamperi, S. & Carozzi, S. Interferon-gamma (IFN-gamma) as in vitro enhancing factor of peritoneal macrophage defective bactericidal activity during continuous ambulatory peritoneal dialysis (CAPD). American Journal of Kidney Diseases 11, 225–30 (1988).
Wang, H. & Lin, C. Interleukin-12 and -18 levels in peritoneal dialysate effluent correlate with the outcome of peritonitis in patients undergoing peritoneal dialysis: implications for the Type I/Type II T-cell immune response. American Journal of Kidney Diseases 46, 328–38 (2005).
Liappas, G. et al. T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage. Biomed Res Int 2015, 416480 (2015).
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Copyright (c) 2024 João Grilo, Catarina Reis Santos, Joana Coutinho, Inês Barreto, Raquel Chorão, Rui Alves Filipe, Andreia Monteiro, Mafalda Fonseca, Ernesto Rocha (Author)
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