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Dysregulated naive B cells and de novo autoreactivity in severe COVID-19.
Woodruff, Matthew C; Ramonell, Richard P; Haddad, Natalie S; Anam, Fabliha A; Rudolph, Mark E; Walker, Tiffany A; Truong, Alexander D; Dixit, Adviteeya N; Han, Jenny E; Cabrera-Mora, Monica; Runnstrom, Martin C; Bugrovsky, Regina; Hom, Jennifer; Connolly, Erin C; Albizua, Igor; Javia, Vidhi; Cashman, Kevin S; Nguyen, Doan C; Kyu, Shuya; Singh Saini, Ankur; Piazza, Michael; Tipton, Christopher M; Khosroshahi, Arezou; Gibson, Greg; Martin, Greg S; Maier, Cheryl L; Esper, Annette; Jenks, Scott A; Lee, F Eun-Hyung; Sanz, Ignacio.
  • Woodruff MC; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.
  • Ramonell RP; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.
  • Haddad NS; Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
  • Anam FA; MicroB-plex, Atlanta, GA, USA.
  • Rudolph ME; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.
  • Walker TA; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.
  • Truong AD; Exagen Inc., Vista, CA, USA.
  • Dixit AN; Department of Medicine, Division of General Internal Medicine, Emory University, Atlanta, GA, USA.
  • Han JE; Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA, USA.
  • Cabrera-Mora M; Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA, USA.
  • Runnstrom MC; Department of Medicine, Division of General Internal Medicine, Emory University, Atlanta, GA, USA.
  • Bugrovsky R; Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA, USA.
  • Hom J; Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA, USA.
  • Connolly EC; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.
  • Albizua I; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.
  • Javia V; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.
  • Cashman KS; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.
  • Nguyen DC; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
  • Kyu S; Department of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Emory University School of Medicine, Emory University, Atlanta, GA, USA.
  • Singh Saini A; Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA, USA.
  • Piazza M; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.
  • Tipton CM; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.
  • Khosroshahi A; Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA, USA.
  • Gibson G; Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA, USA.
  • Martin GS; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.
  • Maier CL; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.
  • Esper A; Nicoya, Kitchener-Waterloo, Ontario, Canada.
  • Jenks SA; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.
  • Lee FE; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.
  • Sanz I; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.
Nature ; 611(7934): 139-147, 2022 11.
Статья в английский | MEDLINE | ID: covidwho-2016757
ABSTRACT
Severe SARS-CoV-2 infection1 has been associated with highly inflammatory immune activation since the earliest days of the COVID-19 pandemic2-5. More recently, these responses have been associated with the emergence of self-reactive antibodies with pathologic potential6-10, although their origins and resolution have remained unclear11. Previously, we and others have identified extrafollicular B cell activation, a pathway associated with the formation of new autoreactive antibodies in chronic autoimmunity12,13, as a dominant feature of severe and critical COVID-19 (refs. 14-18). Here, using single-cell B cell repertoire analysis of patients with mild and severe disease, we identify the expansion of a naive-derived, low-mutation IgG1 population of antibody-secreting cells (ASCs) reflecting features of low selective pressure. These features correlate with progressive, broad, clinically relevant autoreactivity, particularly directed against nuclear antigens and carbamylated proteins, emerging 10-15 days after the onset of symptoms. Detailed analysis of the low-selection compartment shows a high frequency of clonotypes specific for both SARS-CoV-2 and autoantigens, including pathogenic autoantibodies against the glomerular basement membrane. We further identify the contraction of this pathway on recovery, re-establishment of tolerance standards and concomitant loss of acute-derived ASCs irrespective of antigen specificity. However, serological autoreactivity persists in a subset of patients with postacute sequelae, raising important questions as to the contribution of emerging autoreactivity to continuing symptomology on recovery. In summary, this study demonstrates the origins, breadth and resolution of autoreactivity in severe COVID-19, with implications for early intervention and the treatment of patients with post-COVID sequelae.
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Полный текст: Имеется в наличии Коллекция: Международные базы данных база данных: MEDLINE Основная тема: Autoantibodies / B-Lymphocytes / COVID-19 Тип исследования: Прогностическое исследование Темы: Длинный Ковид Пределы темы: Люди Язык: английский Журнал: Nature Год: 2022 Тип: Статья Аффилированная страна: S41586-022-05273-0

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Полный текст: Имеется в наличии Коллекция: Международные базы данных база данных: MEDLINE Основная тема: Autoantibodies / B-Lymphocytes / COVID-19 Тип исследования: Прогностическое исследование Темы: Длинный Ковид Пределы темы: Люди Язык: английский Журнал: Nature Год: 2022 Тип: Статья Аффилированная страна: S41586-022-05273-0