Ann Lab Med.  2023 Sep;43(5):451-460. 10.3343/alm.2023.43.5.451.

Effect of Lymphocyte Phenotypic Alterations on the Humoral Response to Vaccination Against SARS-COV-2 in Dialysis Patients

• Lioulios G
• Fylaktou A
• Asouchidou D
• Xochelli A
• Nikolaidou V
• Stai S
• Christodoulou M
• Giamalis P
• Tsouchnikas I
• Papagianni A
• Stangou M

• KMID: 2551993
• DOI: http://doi.org/10.3343/alm.2023.43.5.451

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.

Keyword

End-stage renal disease; COVID-19 vaccination; BNT162b2; Immune senescence; Hemodiafiltration

Figure

• 

  Fig. 1 Antibody titers at T1, T2, and T3. (A) Anti-RBD values are presented in units of AU/mL, and (B) NAb values are presented in units of μg/mL. Total number of patients and numbers of responders at each time point are shown in the table below. Responders were defined as patients with an RBD titer >1.0 AU/mL and an NAb titer >0.3 μg/mL. **P<0.005. Abbreviations: T1, 30 days after vaccination; T2, 60 days after vaccination; T3, 120 days after vaccination; RBD, receptor-binding domain; NAb, neutralizing antibody.

• 

  Fig. 2 Antibody titers at T1, T2, and T3. (A) Anti-RBD (AU/mL) in patients without DM (non-DM) in comparison to that in patients with DM (positive RBD titer >1.0 AU/mL in 41/43, 39/43, and 38/43 non-DM patients and in 11/11, 11/11, and 9/11 DM patients at T1, T2, and T3, respectively). (B) NAbs (μg/mL) in non-DM patients and DM patients (positive NAb titer > 0.3 μg/mL in 35/43, 32/43, and 27/43 non-DM patients and in 9/11, 9/11, and 2/11 DM patients at T1, T2, and T3, respectively). (C) Anti-RBD (AU/mL) in patients undergoing HD and HDF (positive RBD titer >1.0 AU/mL in 29/30, 29/30, and 27/30 HD patients and in 23/24, 21/24, and 20/24 HDF patients at T1, T2, and T3, respectively). (D) NAbs (μg/mL) in patients undergoing HD and HDF (positive NAb titer >0.3 μg/mL in 24/30, 21/30, and 14/30 HD patients and in 20/24, 20/24, and 15/24 HDF patients at T1, T2, and T3, respectively). *P<0.05, **P<0.005. Abbreviations: T1, 30 days after vaccination; T2, 60 days after vaccination; T3, 120 days after vaccination; RBD, receptor-binding domain; NAb, neutralizing antibody; DM, diabetes mellitus; HD, hemodialysis; HDF, hemodiafiltration; NS, not significant (P>0.05).

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