Low switched memory B cells are associated with no humoral response after SARS-CoV-2 vaccine boosters in kidney transplant recipients

Frontiers in Immunology

Immunology

Ana Guerisoli¹  Federico Yandián¹  Oscar Noboa¹  José Santiago¹  Rossana Astesiano¹  Marcelo Nin²  Mariana Seija³  Javier Noboa⁴  Sergio Orihuela⁵  Natalia Orihuela⁵  Lilian Curi⁵  Catherine Zulberti⁵  Danilo Machado⁶  Emma Bugstaller⁶  Cecilia Recalde⁶  Sergio Bianchi⁷  Florencia Rammauro⁸  Adriana Tiscornia⁹  Daniela Lens^1,10  Joaquin García-Luna^1,10  Natalia Trías^1,10  Andreína Brugnini^1,10 

[1] Centro de Nefrología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay;Centro de Nefrología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay;Centro de Trasplante INU, Hospital Italiano, Montevideo, Uruguay;Centro de Nefrología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay;Departamento de Fisiopatología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay;Centro de Nefrología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay;Departamento de Inmunobiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay;Centro de Trasplante INU, Hospital Italiano, Montevideo, Uruguay;Centro de Trasplante, Hospital Evangélico, Montevideo, Uruguay;Departamento de Fisiopatología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay;Institut Pasteur de Montevideo, Montevideo, Uruguay;Departamento de Inmunobiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay;Institut Pasteur de Montevideo, Montevideo, Uruguay;Instituto Nacional de Donación y Trasplante, Hospital de Clínicas, Facultad de Medicina, Universidad de la República y Ministerio de Salud Pública, Montevideo, Uruguay;Laboratorio de Citometría de Flujo, Departamento Básico de Medicina, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay;

关键词: SARS-CoV-2;    vaccine;    boosters;    kidney transplant;    memory B cell;   

DOI  :  10.3389/fimmu.2023.1202630

 received in 2023-04-09, accepted in 2023-10-09,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionThe humoral response after SARS-CoV-2 vaccination and boosters in kidney transplant recipients (KTRs) is heterogeneous and depends on immunosuppression status. There is no validated immune measurement associated with serological response in clinical practice. Multicolor flow cytometric immunophenotyping could be useful for measuring immune response. This study aimed to study B- and T-cell compartments through Standardized EuroFlow PID Orientation after SARS-CoV-2 vaccination and their association with IgG SARS-CoV-2 seropositivity status after two doses or boosters.MethodsWe conducted a multicenter prospective study to evaluate humoral response after SARS-CoV-2 vaccination in KTRs. Heterologous regimen: two doses of inactivated SARS-CoV-2 and two boosters of BNT162b2 mRNA (n=75). Homologous vaccination: two doses of BNT162b2 mRNA and one BNT162b2 mRNA booster (n=13). Booster doses were administrated to KTRs without taking into account their IgG SARS-CoV-2 seropositivity status. Peripheral blood samples were collected 30 days after the second dose and after the last heterologous or homologous booster. A standardized EuroFlow PID Orientation Tube (PIDOT) and a supervised automated analysis were used for immune monitoring cellular subsets after boosters.ResultsA total of 88 KTRs were included and divided into three groups according to the time of the first detected IgG SARS-CoV-2 seropositivity: non-responders (NRs, n=23), booster responders (BRs, n=41), and two-dose responders (2DRs, n=24). The NR group was more frequent on mycophenolate than the responder groups (NRs, 96%; BRs, 80%; 2DRs, 42%; p=0.000). Switched memory B cells in the 2DR group were higher than those in the BR and NR groups (medians of 30, 17, and 10 cells/ul, respectively; p=0.017). Additionally, the absolute count of central memory/terminal memory CD8 T cells was higher in the 2DR group than in the BR and NR groups. (166, 98, and 93 cells/ul, respectively; p=0.041). The rest of the T-cell populations studied did not show a statistical difference.Conclusionswitched memory B cells and memory CD8 T-cell populations in peripheral blood were associated with the magnitude of the humoral response after SARS-CoV-2 vaccination. Boosters increased IgG anti-SARS-CoV-2 levels, CM/TM CD8 T cells, and switched MBCs in patients with seropositivity after two doses. Interestingly, no seropositivity after boosters was associated with the use of mycophenolate and a lower number of switched MBCs and CM/TM CD8 T cells in peripheral blood.

【 授权许可】

Unknown   
Copyright © 2023 Seija, García-Luna, Rammauro, Brugnini, Trías, Astesiano, Santiago, Orihuela, Zulberti, Machado, Recalde, Yandián, Guerisoli, Noboa, Orihuela, Curi, Bugstaller, Noboa, Nin, Bianchi, Tiscornia and Lens