TitleCVID enteropathy is characterized by exceeding low mucosal IgA levels and interferon-driven inflammation possibly related to the presence of a pathobiont.
Publication TypeJournal Article
Year of Publication2018
AuthorsShulzhenko, N, Dong, X, Vyshenska, D, Greer, RL, Gurung, M, Vasquez-Perez, S, Peremyslova, E, Sosnovtsev, S, Quezado, M, Yao, M, Montgomery-Recht, K, Strober, W, Fuss, IJ, Morgun, A
JournalClin Immunol
Date Published2018 12
KeywordsAcinetobacter baumannii, Common Variable Immunodeficiency, Down-Regulation, Duodenitis, Female, Gastrointestinal Microbiome, Gene Expression, Humans, Immunity, Mucosal, Immunoglobulin A, Inflammation, Interferons, Lipid Metabolism, Malabsorption Syndromes, Male, RNA, Bacterial, RNA, Ribosomal, 16S

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.

Alternate JournalClin Immunol
PubMed ID30240602
PubMed Central IDPMC6289276
Grant ListHHSN261200800001C / RC / CCR NIH HHS / United States
HHSN261200800001E / CA / NCI NIH HHS / United States
R01 DK103761 / DK / NIDDK NIH HHS / United States
U01 AI109695 / AI / NIAID NIH HHS / United States