Immune response to influenza vaccination in ESRD patients undergoing hemodialysis vs. hemodiafiltration

Arkom Nongnuch, Wattanachai Ngampongpan, Sirawat Srichatrapimuk, Artit Wongsa, Sutheera Thongpraphai, Chompunuch Boonarkart, Nutaporn Sanmeema, Malinee Chittaganpitch, Prasert Auewarakul, Boonrat Tassaneetrithep, Andrew Davenport, Angsana Phuphuakrat, Arkom Nongnuch, Wattanachai Ngampongpan, Sirawat Srichatrapimuk, Artit Wongsa, Sutheera Thongpraphai, Chompunuch Boonarkart, Nutaporn Sanmeema, Malinee Chittaganpitch, Prasert Auewarakul, Boonrat Tassaneetrithep, Andrew Davenport, Angsana Phuphuakrat

Abstract

Background: On-line hemodiafiltration (HDF) clears more azotemic toxins compared to high-flux hemodialysis (HD). The response to vaccination is impaired in dialysis patients. We wished to determine whether the immune responses to influenza vaccine in dialysis patients treated by HDF were stronger than those treated by HD.

Materials and methods: We conducted a prospective cohort study in chronic dialysis patients during the 2016 and 2017 influenza seasons. All participants received a single standard dose of trivalent influenza vaccine, and we studied the elicited humoral immune response by hemagglutination inhibition test, and cell-mediated immune response by enumeration of lymphocyte cellular markers and proliferation assays.

Results: We immunized 60 end-stage renal disease (ESRD) patients: 42 (70%) treated with HD and 18 patients (30%) with HDF. The median (interquartile range) age was 65.0 (55.0-74.5) years. All patients developed seroprotection to at least one influenza vaccine strain at one month post-vaccination, and did not differ between groups. By logistic regression, age was the only factor independently associated with seroconversion to all vaccine strains (odds ratio 0.89, 95% confidence interval 0.80-0.98; p = 0.022). Seroprotection to all vaccine strains was sustained for longer in patients treated with HDF, and the results remained the same after age adjustment. For cellular immune response, patients who seroconverted to all vaccine strains had higher CD38+ T cell subpopulations pre-vaccination. Patients treated by HDF had higher lymphocyte proliferation to circulating influenza A strains.

Conclusions: Seroconversion to all influenza vaccine strains was associated with age. Patients treated with HDF demonstrated seroprotection was sustained for longer compared to those treated by HD and greater lymphocyte proliferation to circulating influenza A strains. These encouraging results for HDF require confirmation in a larger dialysis population.

Trial registration: ClinicalTrial.gov, NCT04122222.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Study enrollment and follow-up through…
Fig 1. Study enrollment and follow-up through month 12.
Fig 2. Proportion of participants who had…
Fig 2. Proportion of participants who had seroconversion at month 1 to influenza H1N1 pandemic, H3N2, and B.
Fig 3
Fig 3
Proportion of participants who seroconverted to at least one or all of the three vaccine strains at 1 month post-vaccination (A), and proportion of participants with seroprotection to at least 1 or all three of the vaccine strains at 1 month post-vaccination (B).
Fig 4
Fig 4
Proportion of participants who had seroprotection to all vaccine strains pre-vaccination (mo 0), and post-vaccination at months 1 (mo 1), 6 (mo 6), and 12 (mo 12) (A) HD, (B) HDF.
Fig 5. CD38+ T cell subpopulations at…
Fig 5. CD38+ T cell subpopulations at pre-vaccination.
Effector memory (TEM, CD45RA+CCR7-), central memory (TCM, CD45RA-CCR7+), and naive (CD45RA+CCR7+) T cell subpopulations are shown.
Fig 6. Age-adjusted percentage of T cell…
Fig 6. Age-adjusted percentage of T cell subpopulations at pre-vaccination and post-vaccination.
Fig 7. Lymphocyte proliferation assays to circulating…
Fig 7. Lymphocyte proliferation assays to circulating strains of influenza viruses.
Fold increases of lymphocyte proliferation as compared to pre-vaccination are shown.

References

    1. Descamps-Latscha B. The immune system in end-stage renal disease. Curr Opin Nephrol Hypertens. 1993; 2(6): 883–91. 10.1097/00041552-199311000-00005
    1. Hauser AB, Stinghen AE, Kato S, Bucharles S, Aita C, Yuzawa Y, et al. Characteristics and causes of immune dysfunction related to uremia and dialysis. Perit Dial Int. 2008; 28 Suppl 3: S183–7.
    1. 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(5): 1526–33. 10.2215/CJN.00950208
    1. Cohen G, Horl WH. Immune dysfunction in uremia; an update. Toxins (Basel). 2012; 4(11): 962–90. 10.3390/toxins4110962
    1. Girndt M, Sester M, Sester U, Kaul H, Kohler H. Molecular aspects of T- and B-cell function in uremia. Kidney Int Suppl. 2001; 78: S206–11. 10.1046/j.1523-1755.2001.59780206.x
    1. Meijers RW, Litjens NH, de Wit EA, Langerak AW, van der Spek A, Baan CC, et al. Uremia causes premature ageing of the T cell compartment in end-stage renal disease patients. Immun Ageing. 2012; 9(1): 19 10.1186/1742-4933-9-19
    1. Anding K, Gross P, Rost JM, Allgaier D, Jacobs E. The influence of uraemia and haemodialysis on neutrophil phagocytosis and antimicrobial killing. Nephrol Dial Transplant. 2003; 18(10): 2067–73. 10.1093/ndt/gfg330
    1. Lim WH, Kireta S, Leedham E, Russ GR, Coates PT. Uremia impairs monocyte and monocyte-derived dendritic cell function in hemodialysis patients. Kidney Int. 2007; 72(9): 1138–48. 10.1038/sj.ki.5002425
    1. Sester U, Sester M, Hauk M, Kaul H, Kohler H, Girndt M. T-cell activation follows Th1 rather than Th2 pattern in haemodialysis patients. Nephrol Dial Transplant. 2000; 15(8): 1217–23. 10.1093/ndt/15.8.1217
    1. Fernandez-Fresnedo G, Ramos MA, Gonzalez-Pardo MC, de Francisco AL, Lopez-Hoyos M, Arias M. B lymphopenia in uremia is related to an accelerated in vitro apoptosis and dysregulation of Bcl-2. Nephrol Dial Transplant. 2000; 15(4): 502–10. 10.1093/ndt/15.4.502
    1. Chou CY, Wang SM, Liang CC, Chang CT, Liu JH, Wang IK, et al. Risk of pneumonia among patients with chronic kidney disease in outpatient and inpatient settings: a nationwide population-based study. Medicine (Baltimore). 2014; 93(27): e174 10.1097/MD.0000000000000174
    1. Collins AJ, Foley RN, Gilbertson DT, Chen SC. The state of chronic kidney disease, ESRD, and morbidity and mortality in the first year of dialysis. Clin J Am Soc Nephrol. 2009; 4 Suppl 1: S5–11. 10.2215/CJN.05980809
    1. Viasus D, Garcia-Vidal C, Cruzado JM, Adamuz J, Verdaguer R, Manresa F, et al. Epidemiology, clinical features and outcomes of pneumonia in patients with chronic kidney disease. Nephrol Dial Transplant. 2011; 26(9): 2899–906. 10.1093/ndt/gfq798
    1. Sarnak MJ, Jaber BL. Pulmonary infectious mortality among patients with end-stage renal disease. Chest. 2001; 120(6): 1883–7. 10.1378/chest.120.6.1883
    1. Nordio M, Limido A, Maggiore U, Nichelatti M, Postorino M, Quintaliani G, et al. Survival in patients treated by long-term dialysis compared with the general population. Am J Kidney Dis. 2012; 59(6): 819–28. 10.1053/j.ajkd.2011.12.023
    1. Allon M, Depner TA, Radeva M, Bailey J, Beddhu S, Butterly D, et al. Impact of dialysis dose and membrane on infection-related hospitalization and death: results of the HEMO Study. J Am Soc Nephrol. 2003; 14(7): 1863–70. 10.1097/01.asn.0000074237.78764.d1
    1. Carracedo J, Merino A, Nogueras S, Carretero D, Berdud I, Ramirez R, et al. On-line hemodiafiltration reduces the proinflammatory CD14+CD16+ monocyte-derived dendritic cells: A prospective, crossover study. J Am Soc Nephrol. 2006; 17(8): 2315–21. 10.1681/ASN.2006020105
    1. den Hoedt CH, Grooteman MP, Bots ML, Blankestijn PJ, van der Tweel I, van der Weerd NC, et al. The Effect of Online Hemodiafiltration on Infections: Results from the CONvective TRAnsport STudy. PLoS One. 2015; 10(8): e0135908 10.1371/journal.pone.0135908
    1. DaRoza G, Loewen A, Djurdjev O, Love J, Kempston C, Burnett S, et al. Stage of chronic kidney disease predicts seroconversion after hepatitis B immunization: earlier is better. Am J Kidney Dis. 2003; 42(6): 1184–92. 10.1053/j.ajkd.2003.08.019
    1. Dede F, Yildiz A, Ayli D, Colak N, Odabas AR, Akoglu H, et al. Modulation of the immune response to HBV vaccination by hemodialysis membranes. Int Urol Nephrol. 2010; 42(4): 1069–75. 10.1007/s11255-009-9616-z
    1. Mostovaya IM, Blankestijn PJ, Bots ML, Covic A, Davenport A, Grooteman MP, et al. Clinical evidence on hemodiafiltration: a systematic review and a meta-analysis. Semin Dial. 2014; 27(2): 119–27. 10.1111/sdi.12200
    1. den Hoedt CH, Bots ML, Grooteman MP, van der Weerd NC, Mazairac AH, Penne EL, et al. Online hemodiafiltration reduces systemic inflammation compared to low-flux hemodialysis. Kidney Int. 2014; 86(2): 423–32. 10.1038/ki.2014.9
    1. Rama I, Llaudo I, Fontova P, Cerezo G, Soto C, Javierre C, et al. Online Haemodiafiltration Improves Inflammatory State in Dialysis Patients: A Longitudinal Study. PLoS One. 2016; 11(10): e0164969 10.1371/journal.pone.0164969
    1. Eiselt J, Kielberger L, Rajdl D, Racek J, Pazdiora P, Malanova L. Previous Vaccination and Age are More Important Predictors of Immune Response to Influenza Vaccine than Inflammation and Iron Status in Dialysis Patients. Kidney Blood Press Res. 2016; 41(2): 139–47. 10.1159/000443416
    1. Young B, Zhao X, Cook AR, Parry CM, Wilder-Smith A, MC IC. Do antibody responses to the influenza vaccine persist year-round in the elderly? A systematic review and meta-analysis. Vaccine. 2017; 35(2): 212–21. 10.1016/j.vaccine.2016.11.013
    1. Betjes MG, Langerak AW, van der Spek A, de Wit EA, Litjens NH. Premature aging of circulating T cells in patients with end-stage renal disease. Kidney Int. 2011; 80(2): 208–17. 10.1038/ki.2011.110
    1. Crespo M, Collado S, Mir M, Cao H, Barbosa F, Serra C, et al. Efficacy of influenza A H1N1/2009 vaccine in hemodialysis and kidney transplant patients. Clin J Am Soc Nephrol. 2011; 6(9): 2208–14. 10.2215/CJN.02160311
    1. Ausiello CM, la Sala A, Ramoni C, Urbani F, Funaro A, Malavasi F. Secretion of IFN-gamma, IL-6, granulocyte-macrophage colony-stimulating factor and IL-10 cytokines after activation of human purified T lymphocytes upon CD38 ligation. Cell Immunol. 1996; 173(2): 192–7. 10.1006/cimm.1996.0267
    1. Zupo S, Rugari E, Dono M, Taborelli G, Malavasi F, Ferrarini M. CD38 signaling by agonistic monoclonal antibody prevents apoptosis of human germinal center B cells. Eur J Immunol. 1994; 24(5): 1218–22. 10.1002/eji.1830240532
    1. Moro-Garcia MA, Alonso-Arias R, Lopez-Larrea C. When Aging Reaches CD4+ T-Cells: Phenotypic and Functional Changes. Front Immunol. 2013; 4: 107 10.3389/fimmu.2013.00107
    1. Xiaoyan J, Rongyi C, Xuesen C, Jianzhou Z, Jun J, Xiaoqiang D, et al. The difference of T cell phenotypes in end stage renal disease patients under different dialysis modality. BMC Nephrol. 2019; 20(1): 301 10.1186/s12882-019-1475-y
    1. Ducloux D, Legendre M, Bamoulid J, Rebibou JM, Saas P, Courivaud C, et al. ESRD-associated immune phenotype depends on dialysis modality and iron status: clinical implications. Immun Ageing. 2018; 15: 16 10.1186/s12979-018-0121-z
    1. Valkenburg SA, Li OTW, Li A, Bull M, Waldmann TA, Perera LP, et al. Protection by universal influenza vaccine is mediated by memory CD4 T cells. Vaccine. 2018; 36(29): 4198–206. 10.1016/j.vaccine.2018.06.007
    1. Co MD, Orphin L, Cruz J, Pazoles P, Rothman AL, Ennis FA, et al. Discordance between antibody and T cell responses in recipients of trivalent inactivated influenza vaccine. Vaccine. 2008; 26(16): 1990–8. 10.1016/j.vaccine.2008.02.024

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅