The Humoral Immune Response to BNT162b2 Vaccine Is Associated With Circulating CD19+ B Lymphocytes and the Naïve CD45RA to Memory CD45RO CD4+ T Helper Cells Ratio in Hemodialysis Patients and Kidney Transplant Recipients

Anila Duni; Georgios S Markopoulos; Ioannis Mallioras; Haralampos Pappas; Efthymios Pappas; Vasileios Koutlas; Eirini Tzalavra; Gerasimos Baxevanos; Silvia Priska; Konstantina Gartzonika; Michael Mitsis; Evangelia Dounousi

doi:10.3389/fimmu.2021.760249

The Humoral Immune Response to BNT162b2 Vaccine Is Associated With Circulating CD19+ B Lymphocytes and the Naïve CD45RA to Memory CD45RO CD4+ T Helper Cells Ratio in Hemodialysis Patients and Kidney Transplant Recipients

Front Immunol. 2021 Dec 3:12:760249. doi: 10.3389/fimmu.2021.760249. eCollection 2021.

Authors

Anila Duni^{1

2}, Georgios S Markopoulos³, Ioannis Mallioras¹, Haralampos Pappas^{1

2}, Efthymios Pappas⁴, Vasileios Koutlas², Eirini Tzalavra², Gerasimos Baxevanos^{3

5}, Silvia Priska⁶, Konstantina Gartzonika⁷, Michael Mitsis², Evangelia Dounousi^{1

2

6}

Affiliations

¹ Department of Nephrology, University Hospital of Ioannina, Ioannina, Greece.
² Department of Surgery and Kidney Transplant Unit, University Hospital of Ioannina, Ioannina, Greece.
³ Laboratory of Hematology - Unit of Molecular Biology, University Hospital of Ioannina, Ioannina, Greece.
⁴ Renal Unit, General Hospital of Filiates, Filiates, Greece.
⁵ Internal Medicine Department, Hatzikosta General Hospital of Ioannina, Ioannina, Greece.
⁶ Department of Nephrology, School of Medicine, University of Ioannina, Ioannina, Greece.
⁷ Microbiology Laboratory, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece.

Abstract

Background: The humoral and cellular immune responses to SARS-COV-2 vaccination remain to be elucidated in hemodialysis (HD) patients and kidney transplant recipients (KTRs), considering their baseline immunosuppressed status. The aim of our study was to assess the associations of vaccine-induced antibody responses with circulating lymphocytes sub-populations and their respective patterns of alterations in maintenance HD patients and KTRs.

Materials and methods: We included 34 HD patients and 54 KTRs who received two doses of the mRNA-vaccine BNT162b2. Lymphocyte subpopulations were analyzed by flow cytometry before vaccination (T0), before the second vaccine dose (T1) and 2 weeks after the second dose (T2). The anti-SARS-CoV2 antibody response was assessed at T1 and at T2.

Results: 31 HD patients (91.8%) and 16 KTRs (29.6%) became seropositive at T2. HD patients who became seropositive following the first dose displayed higher CD19+ B lymphocytes compared to their seronegative HD counterparts. A positive correlation was established between CD19+ B cells counts and antibody titers at all time-points in both groups (p < 0.001). KTRs showed higher naïve CD4+CD45RA+ T helper cells compared to HD patients at baseline and T2 whereas HD patients displayed higher memory CD45RO+ T cells compared to KTRs at T2. The naïve CD4+CD45RA to memory CD4+CD45RO+ T helper cells fraction was negatively associated with antibody production in both groups.

Conclusions: Our study provides a potential conceptual framework for monitoring vaccination efficacy in HD patients and KTRs considering the correlation established between CD19+ B cells, generation of memory CD4+ T helper cells and anti SARS-CoV2 antibody response to vaccination.

Keywords: CD19+ B lymphocytes; SARS-COV-2 vaccination; anti-SARS-CoV2 antibodies; hemodialysis; kidney transplant recipients; memory CD4+CD45RO+ T helper cells; naïve CD4+CD45RA+ T helper cells.

MeSH terms

Antibody Formation / immunology*
B-Lymphocytes / immunology*
B-Lymphocytes / metabolism
BNT162 Vaccine / immunology*
Biomarkers
CD4-Positive T-Lymphocytes / immunology*
CD4-Positive T-Lymphocytes / metabolism
COVID-19 / immunology
COVID-19 / virology
COVID-19 Vaccines / immunology
Female
Humans
Immunity, Humoral*
Immunocompromised Host*
Immunologic Memory*
Immunophenotyping
Kidney Transplantation
Lymphocyte Count
Male
Renal Dialysis
SARS-CoV-2 / immunology

Substances

Biomarkers
COVID-19 Vaccines
BNT162 Vaccine