Effect of Lymphocyte Phenotypic Alterations on the Humoral Response to Vaccination Against SARS-COV-2 in Dialysis Patients
0
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Background: The response to vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varies depending on comorbidities. This study evaluated the clinical and immunological factors affecting the humoral response of patients with end-stage renal disease (ESRD) to the BNT162b2 vaccine. Methods: Humoral immunity was evaluated in 54 ESRD patients using serum levels of anti-receptor-binding domain (RBD) and neutralizing antibodies (NAbs), measured by a chemiluminescent immunoassay 30 (T1), 60 (T2), and 120 (T3) days after the second vaccine dose. The results were correlated to baseline patient T- and B-lymphocyte subpopulations determined by flow cytometry. Results: The proportion of seroconverted patients based on the NAb titer decreased from 83.3% at Τ1 to 53.7% at Τ3. Age was negatively correlated to the NAb titer at T1 and Τ2. Patients receiving hemodiafiltration had higher NAb titers at T3. Diabetes was associated with a lower response rate at T3. Univariate analysis revealed a positive correlation between the naïve CD4 T-lymphocyte population and RBD titer at T1 and the NAb titer at T3, with no association observed with naïve CD8 T lymphocytes. NAb titers at T3 were significantly correlated with late-differentiated CD4 T lymphocytes and terminally differentiated effector memory cells re-expressing CD45RA (TEMRA) CD8 T lymphocytes. RBD levels were positively correlated with naïve and memory B-lymphocyte counts at T3. Conclusions: Age, diabetes, and hemodialysis prescription had significant impacts on the response to vaccination. T- and B-lymphocyte phenotypes are major determinants of the humoral response potency to SARS-CoV-2 vaccination with BNT162b2 in patients with ESRD.
Abstract
Background: The response to vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varies depending on comorbidities. This study evaluated the clinical and immunological factors affecting the humoral response of patients with end-stage renal disease (ESRD) to the BNT162b2 vaccine. Methods: Humoral immunity was evaluated in 54 ESRD patients using serum levels of anti-receptor-binding domain (RBD) and neutralizing antibodies (NAbs), measured by a chemiluminescent immunoassay 30 (T1), 60 (T2), and 120 (T3) days after the second vaccine dose. The results were correlated to baseline patient T- and B-lymphocyte subpopulations determined by flow cytometry. Results: The proportion of seroconverted patients based on the NAb titer decreased from 83.3% at Τ1 to 53.7% at Τ3. Age was negatively correlated to the NAb titer at T1 and Τ2. Patients receiving hemodiafiltration had higher NAb titers at T3. Diabetes was associated with a lower response rate at T3. Univariate analysis revealed a positive correlation between the naïve CD4 T-lymphocyte population and RBD titer at T1 and the NAb titer at T3, with no association observed with naïve CD8 T lymphocytes. NAb titers at T3 were significantly correlated with late-differentiated CD4 T lymphocytes and terminally differentiated effector memory cells re-expressing CD45RA (TEMRA) CD8 T lymphocytes. RBD levels were positively correlated with naïve and memory B-lymphocyte counts at T3. Conclusions: Age, diabetes, and hemodialysis prescription had significant impacts on the response to vaccination. T- and B-lymphocyte phenotypes are major determinants of the humoral response potency to SARS-CoV-2 vaccination with BNT162b2 in patients with ESRD.
참고문헌 (40)
- Islam N, "Effects of covid-19 pandemic on life expectancy and premature mortality in 2020 : time series analysis in 37 countries", BMJ, 375, pp.e066768~ (2021)
- Zsichla L, "Risk factors of severe COVID-19: a review of host, viral and environmental factors", Viruses, 15, pp.175~ (2023)
- Mittal A, "COVID-19 pandemic : insights into structure, function, and hACE2 receptor recognition by SARS-CoV-2", PLoS Pathog, 16, pp.e1008762~ (2020)
- Lioulios G, "T cell markers recount the course of immunosenescence in healthy individuals and chronic kidney disease", Clin Immunol, 225, pp.108685~ (2021)
- Cancro MP, "Memory B cells and plasma cells : the differentiative continuum of humoral immunity", Immunol Rev, 303, pp.72~82 (2021)
- Grupper A, "Humoral response to the Pfizer BNT162b2 vaccine in patients undergoing maintenance hemodialysis", Clin J Am Soc Nephrol, 16, pp.1037~1042 (2021)
- Chee YJ, "Dissecting the interaction between COVID-19 and diabetes mellitus", J Diabetes Investig, 11, pp.1104~1114 (2020)
- Yan Z, "COVID-19 vaccinations : a comprehensive review of their safety and efficacy in special populations", Vaccines, 9, pp.1097~ (2021)
- den Hoedt CH, "Online hemodiafiltration reduces systemic inflammation compared to low-flux hemodialysis", Kidney Int, 86, pp.423~432 (2014)
- Lioulios G, "Clustering of end stage renal disease patients by dimensionality reduction algorithms according to lymphocyte senescence markers", Front Immunol, 13, pp.841031~ (2022)
- Vaziri ND, "Gut microbial translocation in the pathogenesis of systemic inflammation in patients with end-stage renal disease", Dig Dis Sci, 59, pp.2020~2022 (2014)
- Cicin-Sain L, "Loss of naive T cells and repertoire constriction predict poor response to vaccination in old primates", J Immunol, 184, pp.6739~6745 (2010)
- Freitas GRR, "Aging and end stage renal disease cause a decrease in absolute circulating lymphocyte counts with a shift to a memory profile and diverge in Treg population", Aging Dis, 10, pp.49~61 (2019)
- Wagner A, "Age-related differences in humoral and cellular immune responses after primary immunisation : indications for stratified vaccination schedules", Sci Rep, 8, pp.9825~ (2018)
- Sampani E, "CD28null and regulatory T cells are substantially disrupted in patients with end-stage renal disease due to diabetes mellitus", Int J Mol Sci, 22, pp.2975~ (2021)
- Bergström M, "Immunological profiling of haemodialysis patients and young healthy individuals with implications for clinical regulatory T cell sorting", Scand J Immunol, 81, pp.318~324 (2015)
- Powell JD, "Molecular regulation of interleukin-2 expression by CD28 co-stimulation and anergy", Immunol Rev, 165, pp.287~300 (1998)
- Callender LA, "Human CD8+ EMRA T cells display a senescence-associated secretory phenotype regulated by p38 MAPK", Aging Cell, 17, pp.e12675~ (2018)
- Spolski R, "Interleukin-21 : a double-edged sword with therapeutic potential", Nat Rev Drug Discov, 13, pp.379~395 (2014)
- Zamauskaite A, "Effect of renal dialysis therapy modality on T cell cytokine production", Nephrol Dial Transplant, 14, pp.49~55 (1999)
- Libetta C, "Polarization of T-helper lymphocytes toward the Th2 phenotype in uremic patients", Am J Kidney Dis, 38, pp.286~295 (2001)
- Mansouri L, "Hemodialysis patients display a declined proportion of Th2 and regulatory T cells in parallel with a high interferon-γ profile", Nephron, 136, pp.254~260 (2017)
- Zold E, "Impaired regulatory T-cell homeostasis due to vitamin D deficiency in undifferentiated connective tissue disease", Scand J Rheumatol, 39, pp.490~497 (2010)
- Charoenngam N, "Immunologic effects of vitamin D on human health and disease", Nutrients, 12, pp.2097~ (2020)
- Agüera ML, "Donor-specific antibodies after starting hemodialysis in nonrenal solid organ transplant recipients : role of TH17", Transplant Proc, 48, pp.2920~2923 (2016)
- Lang CL, "Correlation of interleukin-17-producing effector memory T cells and CD4+CD25+Foxp3 regulatory T cells with the phosphate levels in chronic hemodialysis patients", ScientificWorldJournal, 2014, pp.593170~ (2014)
- De Biasi S, "Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia", Nat Commun, 11, pp.3434~ (2020)
- Gil-Etayo FJ, "An early Th1 response is a key factor for a favorable COVID-19 evolution", Biomedicines, 10, pp.296~ (2022)
- Painter MM, "Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination", Immunity, 54, pp.2133~2142 (2021)
- Lim HW, "Cutting edge : direct suppression of B cells by CD4+ CD25+ regulatory T cells", J Immunol, 175, pp.4180~4183 (2005)
- Garner-Spitzer E, "Tick-borne encephalitis(TBE)and hepatitis B nonresponders feature different immunologic mechanisms in response to TBE and influenza vaccination with involvement of regulatory T and B cells and IL-10", J Immunol, 191, pp.2426~2436 (2013)
- Mathew RO, "Role of T-regulatory cells in the response to hepatitis B vaccine in hemodialysis patients", Hemodial Int, 20, pp.242~252 (2016)
- Goronzy JJ, "Value of immunological markers in predicting responsiveness to influenza vaccination in elderly individuals", J Virol, 75, pp.12182~12187 (2001)
- Saurwein-Teissl M, "Lack of antibody production following immunization in old age : association with CD8(+)CD28(-)T cell clonal expansions and an imbalance in the production of Th1 and Th2 cytokines", J Immunol, 168, pp.5893~5899 (2002)
- Alonso Arias R, "Intensity of the humoral response to cytomegalovirus is associated with the phenotypic and functional status of the immune system", J Virol, 87, pp.4486~4495 (2013)
- Derhovanessian E, "Cytomegalovirus-associated accumulation of late-differentiated CD4 T-cells correlates with poor humoral response to influenza vaccination", Vaccine, 31, pp.685~690 (2013)
- Künzel W, "Kinetics of humoral antibody response to trivalent inactivated split influenza vaccine in subjects previously vaccinated or vaccinated for the first time", Vaccine, 14, pp.1108~1110 (1996)
- Pyhälä R, "HI antibody kinetics in adult volunteers immunized repeatedly with inactivated trivalent influenza vaccine in 1990-1992", Vaccine, 12, pp.947~952 (1994)
- Siegrist CA, "B-cell responses to vaccination at the extremes of age", Nat Rev Immunol, 9, pp.185~194 (2009)
- Gustafson CE, "Influence of immune aging on vaccine responses", J Allergy Clin Immunol, 145, pp.1309~1321 (2020)