tetano
Editor, Senior Moderator
Nat Immunol
. 2020 Oct 7.
doi: 10.1038/s41590-020-00814-z. Online ahead of print.
Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19
Matthew C Woodruff[SUP] 1 2 [/SUP], Richard P Ramonell[SUP] 3 [/SUP], Doan C Nguyen[SUP] 3 [/SUP], Kevin S Cashman[SUP] 1 [/SUP], Ankur Singh Saini[SUP] 1 [/SUP], Natalie S Haddad[SUP] 3 4 [/SUP], Ariel M Ley[SUP] 3 [/SUP], Shuya Kyu[SUP] 3 [/SUP], J Christina Howell[SUP] 5 [/SUP], Tugba Ozturk[SUP] 5 [/SUP], Saeyun Lee[SUP] 1 3 [/SUP], Naveenchandra Suryadevara[SUP] 6 [/SUP], James Brett Case[SUP] 7 [/SUP], Regina Bugrovsky[SUP] 1 [/SUP], Weirong Chen[SUP] 1 [/SUP], Jacob Estrada[SUP] 1 [/SUP], Andrea Morrison-Porter[SUP] 3 [/SUP], Andrew Derrico[SUP] 3 [/SUP], Fabliha A Anam[SUP] 1 [/SUP], Monika Sharma[SUP] 1 [/SUP], Henry M Wu[SUP] 8 [/SUP], Sang N Le[SUP] 1 3 [/SUP], Scott A Jenks[SUP] 1 2 [/SUP], Christopher M Tipton[SUP] 1 2 [/SUP], Bashar Staitieh[SUP] 3 [/SUP], John L Daiss[SUP] 4 [/SUP], Eliver Ghosn[SUP] 1 [/SUP], Michael S Diamond[SUP] 7 9 10 11 [/SUP], Robert H Carnahan[SUP] 6 12 [/SUP], James E Crowe Jr[SUP] 6 12 [/SUP], William T Hu[SUP] 5 [/SUP], F Eun-Hyung Lee[SUP] 13 [/SUP], Ignacio Sanz[SUP] 14 15 [/SUP]
Affiliations
Abstract
A wide spectrum of clinical manifestations has become a hallmark of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, although the immunological underpinnings of diverse disease outcomes remain to be defined. We performed detailed characterization of B cell responses through high-dimensional flow cytometry to reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks of extrafollicular B cell activation and shared B cell repertoire features previously described in autoimmune settings. Extrafollicular activation correlated strongly with large antibody-secreting cell expansion and early production of high concentrations of SARS-CoV-2-specific neutralizing antibodies. Yet, these patients had severe disease with elevated inflammatory biomarkers, multiorgan failure and death. Overall, these findings strongly suggest a pathogenic role for immune activation in subsets of patients with COVID-19. Our study provides further evidence that targeted immunomodulatory therapy may be beneficial in specific patient subpopulations and can be informed by careful immune profiling.
. 2020 Oct 7.
doi: 10.1038/s41590-020-00814-z. Online ahead of print.
Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19
Matthew C Woodruff[SUP] 1 2 [/SUP], Richard P Ramonell[SUP] 3 [/SUP], Doan C Nguyen[SUP] 3 [/SUP], Kevin S Cashman[SUP] 1 [/SUP], Ankur Singh Saini[SUP] 1 [/SUP], Natalie S Haddad[SUP] 3 4 [/SUP], Ariel M Ley[SUP] 3 [/SUP], Shuya Kyu[SUP] 3 [/SUP], J Christina Howell[SUP] 5 [/SUP], Tugba Ozturk[SUP] 5 [/SUP], Saeyun Lee[SUP] 1 3 [/SUP], Naveenchandra Suryadevara[SUP] 6 [/SUP], James Brett Case[SUP] 7 [/SUP], Regina Bugrovsky[SUP] 1 [/SUP], Weirong Chen[SUP] 1 [/SUP], Jacob Estrada[SUP] 1 [/SUP], Andrea Morrison-Porter[SUP] 3 [/SUP], Andrew Derrico[SUP] 3 [/SUP], Fabliha A Anam[SUP] 1 [/SUP], Monika Sharma[SUP] 1 [/SUP], Henry M Wu[SUP] 8 [/SUP], Sang N Le[SUP] 1 3 [/SUP], Scott A Jenks[SUP] 1 2 [/SUP], Christopher M Tipton[SUP] 1 2 [/SUP], Bashar Staitieh[SUP] 3 [/SUP], John L Daiss[SUP] 4 [/SUP], Eliver Ghosn[SUP] 1 [/SUP], Michael S Diamond[SUP] 7 9 10 11 [/SUP], Robert H Carnahan[SUP] 6 12 [/SUP], James E Crowe Jr[SUP] 6 12 [/SUP], William T Hu[SUP] 5 [/SUP], F Eun-Hyung Lee[SUP] 13 [/SUP], Ignacio Sanz[SUP] 14 15 [/SUP]
Affiliations
- PMID: 33028979
- DOI: 10.1038/s41590-020-00814-z
Abstract
A wide spectrum of clinical manifestations has become a hallmark of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, although the immunological underpinnings of diverse disease outcomes remain to be defined. We performed detailed characterization of B cell responses through high-dimensional flow cytometry to reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks of extrafollicular B cell activation and shared B cell repertoire features previously described in autoimmune settings. Extrafollicular activation correlated strongly with large antibody-secreting cell expansion and early production of high concentrations of SARS-CoV-2-specific neutralizing antibodies. Yet, these patients had severe disease with elevated inflammatory biomarkers, multiorgan failure and death. Overall, these findings strongly suggest a pathogenic role for immune activation in subsets of patients with COVID-19. Our study provides further evidence that targeted immunomodulatory therapy may be beneficial in specific patient subpopulations and can be informed by careful immune profiling.