Composition of peripheral blood immune cell compartment in stage 5 chronic kidney disease is affected by smoking and other risk factors associated with systemic inflammatory response
Status In-Process Language English Country Switzerland Media electronic-ecollection
Document type Journal Article
PubMed
40821777
PubMed Central
PMC12353689
DOI
10.3389/fimmu.2025.1608206
Knihovny.cz E-resources
- Keywords
- B cells, T cells, chronic kidney disease, dendritic cells, flow cytometry, inflammation, peripheral blood immune cell composition,
- Publication type
- Journal Article MeSH
BACKGROUND: Stage 5 chronic kidney disease (CKD5) is linked to complex yet not fully understood disturbances in immune system. This study aimed to investigate these disturbances by exploring the detailed composition of peripheral blood immune cell compartments in CKD5 patients and to provide integrative, multivariable dissection of how common inflammatory risk factors shape the immune landscape. METHODS: This cross-sectional study included 107 patients with chronic kidney disease stage 5 (CKD5) and 29 healthy blood donors as controls. Peripheral blood B cells, T cells, and dendritic cells were measured using a standardized and validated flow cytometry panel. The impact of selected clinical factors on immune cell composition was initially evaluated using a robust multivariate method (PERMANOVA). Variables that significantly affected immune cell composition were then included in a subsequent series of Poisson regression models, assessing predictors influence on the counts of individual immune cell subpopulations. RESULTS: Compared to healthy controls, CKD5 patients presented with B cell lymphopenia across all measured subsets except for plasmablasts, T cell lymphopenia with an immunosenescent phenotype predominantly in the CD4+ compartment, and significantly higher counts of LIN-HLA-DR+ antigen-presenting cells, mainly due to an increase in myeloid dendritic cell subpopulations. PERMANOVA identified smoking, CMV seropositivity, age, dialysis treatment, and atherosclerotic cardiovascular disease as factors significantly influencing peripheral blood immune composition. Subsequent Poisson regression models revealed that smoking was associated mainly with an increase in switched memory B cells, CMV seropositivity with an increase in CD4+ and CD8+ TEMRA cells, age with a decrease in naive CD8+ T cells, and dialysis treatment with an increase in marginal-zone B cells. CONCLUSIONS: Patients with CKD5 exhibit distinct composition of peripheral blood immune cells, further modified by other factors associated with systemic inflammatory response. These factors should be considered in immunomonitoring protocols and may enhance prediction of clinical outcomes such as vaccine responses.
Center for Advanced Therapies Charité Universitätsmedizin Berlin Germany
CheckImmune GmbH Campus Virchow Klinikum Berlin Germany
Department of Data Science Institute for Clinical and Experimental Medicine Prague Czechia
Department of Nephrology Institute for Clinical and Experimental Medicine Prague Czechia
Transplantation Laboratory Institute for Clinical and Experimental Medicine Prague Czechia
See more in PubMed
Syed-Ahmed M, Narayanan M. Immune dysfunction and risk of infection in chronic kidney disease. Adv Chronic Kidney Dis. (2019) 26:8–15. doi: 10.1053/j.ackd.2019.01.004, PMID: PubMed DOI
Sarnak M, Jaber B. Mortality caused by sepsis in patients with end-stage renal disease compared with the general population. Kidney Int. (2000) 58:1758–1764. doi: 10.1111/j.1523-1755.2000.00337.x, PMID: PubMed DOI
Kato S, Chmielewski M, Honda H, Pecoits-Filho R, Matsuo S, Yuzawa Y, et al. Aspects of immune dysfunction in end-stage renal disease. Clin J Am Soc Nephrol. (2008) 3:1526–33. doi: 10.2215/CJN.00950208, PMID: PubMed DOI PMC
Recio-Mayoral A, Banerjee D, Streather C, Kaski J. Endothelial dysfunction, inflammation and atherosclerosis in chronic kidney disease–a cross-sectional study of predialysis, dialysis and kidney-transplantation patients. Atherosclerosis. (2011) 216:446–451. doi: 10.1016/j.atherosclerosis.2011.02.017, PMID: PubMed DOI
Stewart J, Vajdic C, van Leeuwen M, Amin J, Webster A, Chapman J, et al. The pattern of excess cancer in dialysis and transplantation. Nephrology dialysis transplantation: Off Publ Eur Dialysis Transplant Assoc - Eur Renal Assoc. (2009) 24:3225–3231. doi: 10.1093/ndt/gfp331, PMID: PubMed DOI
Weiss G, Ganz T, Goodnough L. Anemia of inflammation. Blood. (2019) 133:40–50. Available online at. doi: 10.1182/blood-2018-06-856500, PMID: PubMed DOI PMC
Kaysen GA. Inflammation: cause of vascular disease and malnutrition in dialysis patients. Semin Nephrol. (2004) 24:431–6. doi: 10.1016/j.semnephrol.2004.06.009, PMID: PubMed DOI
Udomkarnjananun S, Takkavatakarn K, Praditpornsilpa K, Nader C, Eiam-Ong S, Jaber BL, et al. Hepatitis B virus vaccine immune response and mortality in dialysis patients: a meta-analysis. J Nephrol. (2020) 33:343–54. doi: 10.1007/s40620-019-00668-1, PMID: PubMed DOI
Mahmoodi M, Aghamohammadi A, Rezaei N, Lessan-Pezeshki M, Pourmand G, Mohagheghi MA, et al. Antibody response to pneumococcal capsular polysaccharide vaccination in patients with chronic kidney disease. Eur Cytokine Netw. (2009) 20:69–74. doi: 10.1684/ecn.2009.0153, PMID: PubMed DOI
Grupper A, Sharon N, Finn T, Cohen R, Israel M, Agbaria A, et al. Humoral response to the pfizer BNT162b2 vaccine in patients undergoing maintenance hemodialysis. Clin J Am Soc Nephrol. (2021) 16(7):1037–1042. doi: 10.2215/CJN.03500321, PMID: PubMed DOI PMC
Stenvinkel P. Inflammation in end-stage renal failure: could it be treated? Nephrol Dialysis Transplantation. (2002) 17:33–8. doi: 10.1093/ndt/17.suppl_8.33, PMID: PubMed DOI
Chiu YL, Shu KH, Yang FJ, Chou TY, Chen PM, Lay FY, et al. A comprehensive characterization of aggravated aging-related changes in T lymphocytes and monocytes in end-stage renal disease: the iESRD study. Immun Ageing. (2018) 15:27. doi: 10.1186/s12979-018-0131-x, PMID: PubMed DOI PMC
Betjes MGH, Langerak AW, van der Spek A, de Wit EA, Litjens NHR. Premature aging of circulating T cells in patients with end-stage renal disease. Kidney Int. (2011) 80:208–17. doi: 10.1038/ki.2011.110, PMID: PubMed DOI
Saule P, Trauet J, Dutriez V, Lekeux V, Dessaint JP, Labalette M. Accumulation of memory T cells from childhood to old age: central and effector memory cells in CD4(+) versus effector memory and terminally differentiated memory cells in CD8(+) compartment. Mech Ageing Dev. (2006) 127:274–81. doi: 10.1016/j.mad.2005.11.001, PMID: PubMed DOI
Bingaman AW, Farber DL. Memory T cells in transplantation: generation, function, and potential role in rejection. Am J Transplantation. (2004) 4:846–52. doi: 10.1111/j.1600-6143.2004.00453.x, PMID: PubMed DOI
Pracovní skupina STL. Doporučení Společnosti pro transfuzní lékařství ČLS JEP: Posuzování způsobilosti k dárcovství krve a krevních složek, verze 11. Společnost pro transfuzní lékařství. (2024). Available online at: https://www.transfuznispolecnost.cz/doporucene-postupyfile-accordion-doporucene-postupy-stl (Accessed June 21, 2025).
Wang H, Peng G, Bai J, He B, Huang K, Hu X, et al. Cytomegalovirus infection and relative risk of cardiovascular disease (Ischemic heart disease, stroke, and cardiovascular death): A meta-analysis of prospective studies up to 2016. J Am Heart Assoc. (2017) 6:e005025. doi: 10.1161/JAHA.116.005025, PMID: PubMed DOI PMC
NHIS . Adult tobacco use - glossary (2019). Available online at: https://www.cdc.gov/nchs/nhis/tobacco/tobacco_glossary.htm (Accessed Nov 30, 2020).
Streitz M, Miloud T, Kapinsky M, Reed MR, Magari R, Geissler EK, et al. Standardization of whole blood immune phenotype monitoring for clinical trials: panels and methods from the ONE study. Transplant Res. (2013) 2:17. doi: 10.1186/2047-1440-2-17, PMID: PubMed DOI PMC
Stranavova L, Hruba P, Slatinska J, Sawitzki B, Reinke P, Volk HD, et al. Dialysis therapy is associated with peripheral marginal zone B-cell augmentation. Transpl Immunol. (2020) 60:101289. doi: 10.1016/j.trim.2020.101289, PMID: PubMed DOI
Oksanen J, Simpson GL, Blanchet FG, Kindt R, Legendre P, Minchin PR, et al. vegan: community ecology package (2024). Available online at: https://cran.r-project.org/web/packages/vegan/index.html (Accessed Oct 8, 2024).
Brooks ME, Kristensen K, van BKJ, Magnusson A, CW B, Nielsen A, et al. glmmTMB balances speed and flexibility among packages for zero-inflated generalized linear mixed modeling. R J. (2017) 9:378–400. doi: 10.32614/RJ-2017-066 DOI
Benjamini Y, Hochberg Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J R Stat Soc Ser B (Methodological). (1995) 57:289–300. doi: 10.1111/j.2517-6161.1995.tb02031.x DOI
Gu Z, Eils R, Schlesner M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics. (2016) 32:2847–9. doi: 10.1093/bioinformatics/btw313, PMID: PubMed DOI
Zahradka I, Tichanek F, Majercikova L, Douskova J, Streitz M, Schlickeiser A, et al. filip-tichanek. In: filip-tichanek/rTX_lymphocytes. Available online at: https://github.com/filip-tichanek/rTX_lymphocytes.
Pahl MV, Gollapudi S, Sepassi L, Gollapudi P, Elahimehr R, Vaziri ND. Effect of end-stage renal disease on B-lymphocyte subpopulations, IL-7, BAFF and BAFF receptor expression. Nephrol Dial Transplant. (2010) 25:205–12. doi: 10.1093/ndt/gfp397, PMID: PubMed DOI PMC
Gaultier GN, McCready W, Ulanova M. Natural immunity against Haemophilus influenzae type a and B-cell subpopulations in adult patients with severe chronic kidney disease. Vaccine. (2019) 37:3677–84. doi: 10.1016/j.vaccine.2019.05.036, PMID: PubMed DOI
Magicova M, Zahradka I, Fialova M, Neskudla T, Gurka J, Modos I, et al. Determinants of immune response to anti-SARS-coV-2 mRNA vaccines in kidney transplant recipients: A prospective cohort study. Transplantation. (2022) 106:842–52. doi: 10.1097/TP.0000000000004044, PMID: PubMed DOI PMC
Petr V, Zahradka I, Modos I, Roder M, Prewett A, Fialova M, et al. First booster of SARS-COV-2 mRNA vaccine is not associated with alloimmunization and subclinical injury of kidney allograft. Transplantation. (2023) 107:e62–4. doi: 10.1097/TP.0000000000004421, PMID: PubMed DOI
Zahradka I, Petr V, Modos I, Magicova M, Dusek L, Viklicky O. Association between SARS-coV-2 messenger RNA vaccines and lower infection rates in kidney transplant recipients: A registry-based report. Ann Intern Med. (2022) 175(7):961–968. doi: 10.7326/M21-2973, PMID: PubMed DOI PMC
David Morgan M, Richter A, Al-Ali S, Flint J, Yiannakis C, Drayson M, et al. Association of low B cell count and igG levels with infection, and poor vaccine response with all-cause mortality in an immunosuppressed vasculitis population. Arthritis Care Res (Hoboken). (2016) 68:853–60. doi: 10.1002/acr.22757, PMID: PubMed DOI
Ghandili S, Schönlein M, Lütgehetmann M, Schulze Zur Wiesch J, Becher H, Bokemeyer C, et al. Post-vaccination anti-SARS-coV-2-antibody response in patients with multiple myeloma correlates with low CD19+ B-lymphocyte count and anti-CD38 treatment. Cancers (Basel). (2021) 13:3800. doi: 10.3390/cancers13153800, PMID: PubMed DOI PMC
Schulz E, Hodl I, Forstner P, Hatzl S, Sareban N, Moritz M, et al. CD19+IgD+CD27- naïve B cells as predictors of humoral response to COVID 19 mRNA vaccination in immunocompromised patients. Front Immunol. (2021) 12:803742. doi: 10.3389/fimmu.2021.803742, PMID: PubMed DOI PMC
van Assen S, Holvast A, Benne CA, Posthumus MD, van Leeuwen MA, Voskuyl AE, et al. Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab. Arthritis Rheumatol. (2010) 62:75–81. doi: 10.1002/art.25033, PMID: PubMed DOI
Svachova V, Sekerkova A, Hruba P, Tycova I, Rodova M, Cecrdlova E, et al. Dynamic changes of B-cell compartments in kidney transplantation: lack of transitional B cells is associated with allograft rejection. Transpl Int. (2016) 29:540–8. doi: 10.1111/tri.12751, PMID: PubMed DOI
Thomas R, Wang W, Su DM. Contributions of age-related thymic involution to immunosenescence and inflammaging. Immun Ageing. (2020) 17:2. doi: 10.1186/s12979-020-0173-8, PMID: PubMed DOI PMC
Kilpatrick RD, Rickabaugh T, Hultin LE, Hultin P, Hausner MA, Detels R, et al. Homeostasis of the naive CD4+ T cell compartment during aging. J Immunol. (2008) 180:1499–507. doi: 10.4049/jimmunol.180.3.1499, PMID: PubMed DOI PMC
Fagnoni FF, Vescovini R, Passeri G, Bologna G, Pedrazzoni M, Lavagetto G, et al. Shortage of circulating naive CD8(+) T cells provides new insights on immunodeficiency in aging. Blood. (2000) 95:2860–8. doi: 10.1182/blood.V95.9.2860.009k35_2860_2868, PMID: PubMed DOI
Weltevrede M, Eilers R, de Melker HE, van Baarle D. Cytomegalovirus persistence and T-cell immunosenescence in people aged fifty and older: A systematic review. Exp Gerontol. (2016) 77:87–95. doi: 10.1016/j.exger.2016.02.005, PMID: PubMed DOI
Doan Ngoc TM, Tilly G, Danger R, Bonizec O, Masset C, Guérif P, et al. Effector memory-expressing CD45RA (TEMRA) CD8+ T cells from kidney transplant recipients exhibit enhanced purinergic P2X4 receptor-dependent proinflammatory and migratory responses. J Am Soc Nephrol. (2022) 33:2211–31. doi: 10.1681/ASN.2022030286, PMID: PubMed DOI PMC
Vaulet T, Callemeyn J, Lamarthée B, Antoranz A, Debyser T, Koshy P, et al. The clinical relevance of the infiltrating immune cell composition in kidney transplant rejection. J Am Soc Nephrology. (2024) 35:886. doi: 10.1681/ASN.0000000000000350, PMID: PubMed DOI PMC
Gerlach UA, Vogt K, Schlickeiser S, Meisel C, Streitz M, Kunkel D, et al. Elevation of CD4+ differentiated memory T cells is associated with acute cellular and antibody-mediated rejection after liver transplantation. Transplantation. (2013) 95:1512–20. doi: 10.1097/TP.0b013e318290de18, PMID: PubMed DOI
Stranavova L, Pelak O, Svaton M, Hruba P, Fronkova E, Slavcev A, et al. Heterologous cytomegalovirus and allo-reactivity by shared T cell receptor repertoire in kidney transplantation. Front Immunol. (2019) 10:2549. doi: 10.3389/fimmu.2019.02549, PMID: PubMed DOI PMC
Kruetzmann S, Rosado MM, Weber H, Germing U, Tournilhac O, Peter HH, et al. Human immunoglobulin M memory B cells controlling Streptococcus pneumoniae infections are generated in the spleen. J Exp Med. (2003) 197:939–45. doi: 10.1084/jem.20022020, PMID: PubMed DOI PMC
Panda S, Ding JL. Natural antibodies bridge innate and adaptive immunity. J Immunol. (2015) 194:13–20. doi: 10.4049/jimmunol.1400844, PMID: PubMed DOI
Cerutti A, Cols M, Puga I. Marginal zone B cells: virtues of innate-like antibody-producing lymphocytes. Nat Rev Immunol. (2013) 13:118–32. doi: 10.1038/nri3383, PMID: PubMed DOI PMC
Hendricks J, Bos NA, Kroese FGM. Heterogeneity of memory marginal zone B cells. Crit Rev Immunol. (2018) 38:145–58. doi: 10.1615/CritRevImmunol.2018024985, PMID: PubMed DOI PMC
Weller S, Braun MC, Tan BK, Rosenwald A, Cordier C, Conley ME, et al. Human blood IgM “memory” B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire. Blood. (2004) 104:3647–54. doi: 10.1182/blood-2004-01-0346, PMID: PubMed DOI PMC
Haller MC, Kainz A, Baer H, Oberbauer R. Dialysis vintage and outcomes after kidney transplantation: A retrospective cohort study. Clin J Am Soc Nephrol. (2017) 12:122–30. doi: 10.2215/CJN.04120416, PMID: PubMed DOI PMC
Gorbacheva V, Fan R, Gaudette B, Baldwin WM, Fairchild RL, Valujskikh A. Marginal zone B cells are required for optimal humoral responses to allograft. Am J Transplant. (2025) 25:48–59. doi: 10.1016/j.ajt.2024.09.004, PMID: PubMed DOI PMC
Weinrauch LA, Claggett B, Liu J, Finn PV, Weir MR, Weiner DE, et al. Smoking and outcomes in kidney transplant recipients: a PubMed DOI PMC
Brandsma CA, Hylkema MN, Geerlings M, van Geffen WH, Postma DS, Timens W, et al. Increased levels of (class switched) memory B cells in peripheral blood of current smokers. Respir Res. (2009) 10:108. doi: 10.1186/1465-9921-10-108, PMID: PubMed DOI PMC
Nogueira JM, Haririan A, Jacobs SC, Cooper M, Weir MR. Cigarette smoking, kidney function, and mortality after live donor kidney transplant. Am J Kidney Diseases. (2010) 55:907–15. doi: 10.1053/j.ajkd.2009.10.058, PMID: PubMed DOI