Caterina E. Faliti, Trinh T. P. Van, Fabliha A. Anam, Narayanaiah Cheedarla, M. Elliott Williams, Ashish Kumar Mishra, Sabeena Y. Usman, Matthew C. Woodruff, Geoff Kraker, Martin C. Runnstrom, Shuya Kyu, Daniel Sanz, Hasan Ahmed, Midushi Ghimire, Andrea Morrison-Porter, Hannah Quehl, Natalie S. Haddad, Weirong Chen, Suneethamma Cheedarla, Andrew S. Neish, John D. Roback, Rustom Antia, Jennifer Hom, Christopher M. Tipton, John M. Lindner, Eliver Ghosn, Surender Khurana, Christopher D. Scharer, Arezou Khosroshahi, F. Eun-Hyung Lee, Ignacio Sanz
{"title":"疾病相关 B 细胞和免疫内型决定了人类系统性红斑狼疮患者对 SARS-CoV-2 mRNA 疫苗接种的适应性免疫反应","authors":"Caterina E. Faliti, Trinh T. P. Van, Fabliha A. Anam, Narayanaiah Cheedarla, M. Elliott Williams, Ashish Kumar Mishra, Sabeena Y. Usman, Matthew C. Woodruff, Geoff Kraker, Martin C. Runnstrom, Shuya Kyu, Daniel Sanz, Hasan Ahmed, Midushi Ghimire, Andrea Morrison-Porter, Hannah Quehl, Natalie S. Haddad, Weirong Chen, Suneethamma Cheedarla, Andrew S. Neish, John D. Roback, Rustom Antia, Jennifer Hom, Christopher M. Tipton, John M. Lindner, Eliver Ghosn, Surender Khurana, Christopher D. Scharer, Arezou Khosroshahi, F. Eun-Hyung Lee, Ignacio Sanz","doi":"10.1038/s41590-024-02010-9","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"71 1","pages":""},"PeriodicalIF":27.7000,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE\",\"authors\":\"Caterina E. Faliti, Trinh T. P. Van, Fabliha A. Anam, Narayanaiah Cheedarla, M. Elliott Williams, Ashish Kumar Mishra, Sabeena Y. Usman, Matthew C. Woodruff, Geoff Kraker, Martin C. Runnstrom, Shuya Kyu, Daniel Sanz, Hasan Ahmed, Midushi Ghimire, Andrea Morrison-Porter, Hannah Quehl, Natalie S. Haddad, Weirong Chen, Suneethamma Cheedarla, Andrew S. Neish, John D. Roback, Rustom Antia, Jennifer Hom, Christopher M. Tipton, John M. Lindner, Eliver Ghosn, Surender Khurana, Christopher D. Scharer, Arezou Khosroshahi, F. Eun-Hyung Lee, Ignacio Sanz\",\"doi\":\"10.1038/s41590-024-02010-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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.</p>\",\"PeriodicalId\":19032,\"journal\":{\"name\":\"Nature Immunology\",\"volume\":\"71 1\",\"pages\":\"\"},\"PeriodicalIF\":27.7000,\"publicationDate\":\"2024-11-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41590-024-02010-9\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41590-024-02010-9","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE
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−CD27− ‘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.
期刊介绍:
Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.