Abstract
Common variable immunodeficiency (CVID), the most common symptomatic primary antibody deficiency, is accompanied in some patients by a duodenal inflammation and malabsorption syndrome known as CVID enteropathy (E-CVID).The goal of this study was to investigate the immunological abnormalities in CVID patients that lead to enteropathy as well as the contribution of intestinal microbiota to this process.We found that, in contrast to noE-CVID patients (without enteropathy), E-CVID patients have exceedingly low levels of IgA in duodenal tissues. In addition, using transkingdom network analysis of the duodenal microbiome, we identified Acinetobacter baumannii as a candidate pathobiont in E-CVID. Finally, we found that E-CVID patients exhibit a pronounced activation of immune genes and down-regulation of epithelial lipid metabolism genes. We conclude that in the virtual absence of mucosal IgA, pathobionts such as A. baumannii, may induce inflammation that re-directs intestinal molecular pathways from lipid metabolism to immune processes responsible for enteropathy.
Citations
Nov 23, 2018·Journal of Clinical Immunology·Silje F JørgensenPål Aukrust
Apr 25, 2019·Reviews in Medical Virology·Timothy P W JonesDavid M Lowe
Aug 8, 2019·Current Opinion in Allergy and Clinical Immunology·Roos-Marijn BerbersHelen Louisa Leavis
Jul 3, 2019·Scientific Reports·Magnhild E MacphersonSilje F Jørgensen
Oct 5, 2019·Gut Microbes·Moriah J CastlemanCara Wilson
Jun 14, 2020·Allergy·Oliver F WirzMübeccel Akdis
Jul 1, 2020·PLoS Pathogens·Mary Melissa RolandJason Lee Kubinak
Aug 29, 2019·Frontiers in Immunology·Kristýna FiedorováTomáš Freiberger
Jul 29, 2020·International Journal of Molecular Sciences·Ida Judyta MaleszaPiotr Eder
Nov 12, 2019·Frontiers in Immunology·Ahmed Dawood MohammedJason L Kubinak
Jan 6, 2021·Nature Communications·Richard R RodriguesNatalia Shulzhenko
Feb 13, 2021·International Journal of Molecular Sciences·Riccardo CastagnoliLuigi Daniele Notarangelo
Mar 27, 2021·Brain Research Bulletin·Jiapeng DengJunhua Yang
Jun 1, 2021·Frontiers in Immunology·Juraj BosákDavid Šmajs
Aug 20, 2021·Frontiers in Immunology·Gilda VarricchiGiuseppe Spadaro
Oct 9, 2021·JCI Insight·Hsi-En HoCharlotte Cunningham-Rundles