tetano
Editor, Senior Moderator
Nat Immunol
. 2024 Nov 12.
doi: 10.1038/s41590-024-02010-9. Online ahead of print. Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE
Caterina E Faliti[SUP] 1 2 [/SUP], Trinh T P Van[SUP] 1 2 [/SUP], Fabliha A Anam[SUP] 1 2 [/SUP], Narayanaiah Cheedarla[SUP] 3 [/SUP], M Elliott Williams[SUP] 4 [/SUP], Ashish Kumar Mishra[SUP] 5 [/SUP], Sabeena Y Usman[SUP] 1 2 [/SUP], Matthew C Woodruff[SUP] 1 2 [/SUP], Geoff Kraker[SUP] 6 [/SUP], Martin C Runnstrom[SUP] 7 [/SUP], Shuya Kyu[SUP] 7 [/SUP], Daniel Sanz[SUP] 1 2 [/SUP], Hasan Ahmed[SUP] 8 [/SUP], Midushi Ghimire[SUP] 1 2 [/SUP], Andrea Morrison-Porter[SUP] 7 [/SUP], Hannah Quehl[SUP] 7 [/SUP], Natalie S Haddad[SUP] 7 9 [/SUP], Weirong Chen[SUP] 1 2 [/SUP], Suneethamma Cheedarla[SUP] 3 [/SUP], Andrew S Neish[SUP] 3 [/SUP], John D Roback[SUP] 3 [/SUP], Rustom Antia[SUP] 8 [/SUP], Jennifer Hom[SUP] 1 2 [/SUP], Christopher M Tipton[SUP] 1 2 [/SUP], John M Lindner[SUP] 10 [/SUP], Eliver Ghosn[SUP] 1 [/SUP], Surender Khurana[SUP] 5 [/SUP], Christopher D Scharer[SUP] 4 [/SUP], Arezou Khosroshahi[SUP] 1 2 [/SUP], F Eun-Hyung Lee[SUP] 7 [/SUP], Ignacio Sanz[SUP] 11 12 [/SUP]
Affiliations
Severe acute respiratory syndrome coronavirus 2 mRNA vaccination has reduced effectiveness in certain immunocompromised individuals. However, the cellular mechanisms underlying these defects, as well as the contribution of disease-induced cellular abnormalities, remain largely unexplored. In this study, we conducted a comprehensive serological and cellular analysis of patients with autoimmune systemic lupus erythematosus (SLE) who received the Wuhan-Hu-1 monovalent mRNA coronavirus disease 2019 vaccine. Our findings revealed that patients with SLE exhibited reduced avidity of anti-receptor-binding domain antibodies, leading to decreased neutralization potency and breadth. We also observed a sustained anti-spike response in IgD[SUP]-[/SUP]CD27[SUP]-[/SUP] 'double-negative (DN)' DN2/DN3 B cell populations persisting during memory responses and with greater representation in the SLE cohort. Additionally, patients with SLE displayed compromised anti-spike T cell immunity. Notably, low vaccine efficacy strongly correlated with higher values of a newly developed extrafollicular B and T cell score, supporting the importance of distinct B cell endotypes. Finally, we found that anti-BAFF blockade through belimumab treatment was associated with poor vaccine immunogenicity due to inhibition of naive B cell priming and an unexpected impact on circulating T follicular helper cells.
. 2024 Nov 12.
doi: 10.1038/s41590-024-02010-9. Online ahead of print. Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE
Caterina E Faliti[SUP] 1 2 [/SUP], Trinh T P Van[SUP] 1 2 [/SUP], Fabliha A Anam[SUP] 1 2 [/SUP], Narayanaiah Cheedarla[SUP] 3 [/SUP], M Elliott Williams[SUP] 4 [/SUP], Ashish Kumar Mishra[SUP] 5 [/SUP], Sabeena Y Usman[SUP] 1 2 [/SUP], Matthew C Woodruff[SUP] 1 2 [/SUP], Geoff Kraker[SUP] 6 [/SUP], Martin C Runnstrom[SUP] 7 [/SUP], Shuya Kyu[SUP] 7 [/SUP], Daniel Sanz[SUP] 1 2 [/SUP], Hasan Ahmed[SUP] 8 [/SUP], Midushi Ghimire[SUP] 1 2 [/SUP], Andrea Morrison-Porter[SUP] 7 [/SUP], Hannah Quehl[SUP] 7 [/SUP], Natalie S Haddad[SUP] 7 9 [/SUP], Weirong Chen[SUP] 1 2 [/SUP], Suneethamma Cheedarla[SUP] 3 [/SUP], Andrew S Neish[SUP] 3 [/SUP], John D Roback[SUP] 3 [/SUP], Rustom Antia[SUP] 8 [/SUP], Jennifer Hom[SUP] 1 2 [/SUP], Christopher M Tipton[SUP] 1 2 [/SUP], John M Lindner[SUP] 10 [/SUP], Eliver Ghosn[SUP] 1 [/SUP], Surender Khurana[SUP] 5 [/SUP], Christopher D Scharer[SUP] 4 [/SUP], Arezou Khosroshahi[SUP] 1 2 [/SUP], F Eun-Hyung Lee[SUP] 7 [/SUP], Ignacio Sanz[SUP] 11 12 [/SUP]
Affiliations
- PMID: 39533072
- DOI: 10.1038/s41590-024-02010-9
Severe acute respiratory syndrome coronavirus 2 mRNA vaccination has reduced effectiveness in certain immunocompromised individuals. However, the cellular mechanisms underlying these defects, as well as the contribution of disease-induced cellular abnormalities, remain largely unexplored. In this study, we conducted a comprehensive serological and cellular analysis of patients with autoimmune systemic lupus erythematosus (SLE) who received the Wuhan-Hu-1 monovalent mRNA coronavirus disease 2019 vaccine. Our findings revealed that patients with SLE exhibited reduced avidity of anti-receptor-binding domain antibodies, leading to decreased neutralization potency and breadth. We also observed a sustained anti-spike response in IgD[SUP]-[/SUP]CD27[SUP]-[/SUP] 'double-negative (DN)' DN2/DN3 B cell populations persisting during memory responses and with greater representation in the SLE cohort. Additionally, patients with SLE displayed compromised anti-spike T cell immunity. Notably, low vaccine efficacy strongly correlated with higher values of a newly developed extrafollicular B and T cell score, supporting the importance of distinct B cell endotypes. Finally, we found that anti-BAFF blockade through belimumab treatment was associated with poor vaccine immunogenicity due to inhibition of naive B cell priming and an unexpected impact on circulating T follicular helper cells.