SARS-CoV-2 Vaccination Responses in Anti-CD20-Treated Progressive Multiple Sclerosis Patients Show Immunosenescence in Antigen-Specific B and T Cells
Abstract
:1. Introduction
2. Methods
2.1. Patient Selection
2.2. Blood Collection and Isolation of Mononuclear Cells
2.3. Activation Induced Cell Marker Assay (AIM) and T Cell Phenotype
2.4. Detection of SARS-CoV-2-Specific B Cells
2.5. Intracellular Cytokine Staining (ICS)
2.6. Computational Analysis of Flow Cytometry Data
2.6.1. T Cell Analysis
2.6.2. B Cell Analysis
2.7. Statistical Analysis
2.8. Principal Component Analysis
3. Results
3.1. MS Patients Undergoing aCD20 Therapy Develop a CD4+ Ag+ Specific T Cell Response Similar to Healthy Donors
3.2. Progressive MS Patients Display High Percentage of CD4+CD107a+ Ag+ Specific T Cell
3.3. Higher Percentage of CD8+ Ag+ T Cells Characterize Progressive Patients
3.4. CD8+ Ag+ T Cells from PR Patients Are Much More Polyfunctional If Compared to Age-Matched HD
3.5. Ag+ B Cell Response Is Low in MS Patients Undergoing aCD20 Treatment, but It Is Still Detectable
3.6. Principal Component Analysis Revealed That Relapsing Remitting and Progressive MS Patients Treated with Anti-CD20 Showed Similar SARS-CoV-2 Immune Features
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Study Population (N = 36) | HD_RR (N = 7) | HD_PR (N = 6) | RR (N = 10) | PR (N = 13) |
---|---|---|---|---|
Age, median (IQR), y | 35.0 (29.0–42.5) | 57.5 (55.5–66.25) | 35.5 (30.25–38.0) | 57.0 (53.0–61.0) |
Females, n (%) | 6.0 (85.7) | 4.0 (66.7) | 6.0 (60.0) | 10.0 (76.9) |
Disease duration, median (IQR), y | ─ | ─ | 11.5 (10.0–12.75) | 17.0 (10.0–24.00) |
Disability by EDSS score, median (IQR) | ─ | ─ | 2.75 (1.25–4.38) | 6.0 (4.00–6.50) |
Time from last treatment starts, median (IQR), y | ─ | ─ | 0.526 (0.50–0.57) | 0.528 (0.50–0.60) |
Time from last infusion to last vaccination, median (IQR), months | ─ | ─ | 3.70 (0.19–4.81) | 3.41 (1.44–4.33) |
Absolute lymphocyte count, median (IQR), 103cells/mm3 | 2.22 (1.95–2.33) | 2.225 (2.23–2.23) | 1.61 (1.38–2.06) | 1.74 (1.49–2.22) |
CD19 B─cell count, median (IQR), n/mm3 | 138,944 (124,511–254,738) | 118,148 (99,847–142,122) | 4381 (1010–11,212) | 7822 (1125–30,770) |
Breakthrough COVID─19 after full vaccination, n (%) | 2.00 (66.70) | NA | 1.00 (10.00) | 2.00 (15.40) |
SARS─CoV─2 IgGII titer after full vaccination, AU/mL | ||||
Median (IQR) | 12,288.50 (5334–16,687.50) | 28,306.60 (7348.60–34,873.30) | 135.65 (41.80–9656) | 1089.1 (9.25–7176.0) |
SARS─CoV─2 RBD IgG titer after full vaccination, AU/mL | ||||
Median (IQR) | 9167.221 (4539.23–13,011.16) | 7829.5923 (6621.08–15,762.73) | 83.02 (4.80–8700.06) | 346.13 (0.41–3760.41) |
Time from first vaccination to sampling, median (IQR), months | 14.25 (9.10–16.56) | 10.71 (7.26–12.83) | 11.67 (9.52–15.40) | 10.94 (9.63–15.01) |
Time from last vaccination to sampling, median (IQR), months | 3.61 (1.74–6.60) | 3.28 (0.92–6.04) | 2.56 (1.695–8.22) | 2.96 (2.20–7.705) |
Type of third vaccine dose | ||||
BNT162b2, n (%) | 5 (71.43%) | 3 (50.00%) | 8 (80.00%) | 9 (69.23%) |
mRNA─1273, n (%) | 2 (28.57%) | 3 (50.00%) | 2 (20.00%) | 4 (30.77%) |
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De Biasi, S.; Ciobanu, A.L.; Santacroce, E.; Lo Tartaro, D.; Degliesposti, G.; D’Angerio, M.; Leccese, M.; Cardi, M.; Trenti, T.; Cuccorese, M.; et al. SARS-CoV-2 Vaccination Responses in Anti-CD20-Treated Progressive Multiple Sclerosis Patients Show Immunosenescence in Antigen-Specific B and T Cells. Vaccines 2024, 12, 924. https://doi.org/10.3390/vaccines12080924
De Biasi S, Ciobanu AL, Santacroce E, Lo Tartaro D, Degliesposti G, D’Angerio M, Leccese M, Cardi M, Trenti T, Cuccorese M, et al. SARS-CoV-2 Vaccination Responses in Anti-CD20-Treated Progressive Multiple Sclerosis Patients Show Immunosenescence in Antigen-Specific B and T Cells. Vaccines. 2024; 12(8):924. https://doi.org/10.3390/vaccines12080924
Chicago/Turabian StyleDe Biasi, Sara, Alin Liviu Ciobanu, Elena Santacroce, Domenico Lo Tartaro, Gianluca Degliesposti, Miriam D’Angerio, Maristella Leccese, Martina Cardi, Tommaso Trenti, Michela Cuccorese, and et al. 2024. "SARS-CoV-2 Vaccination Responses in Anti-CD20-Treated Progressive Multiple Sclerosis Patients Show Immunosenescence in Antigen-Specific B and T Cells" Vaccines 12, no. 8: 924. https://doi.org/10.3390/vaccines12080924