Title | CVID enteropathy is characterized by exceeding low mucosal IgA levels and interferon-driven inflammation possibly related to the presence of a pathobiont. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Shulzhenko, 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 |
Journal | Clin Immunol |
Volume | 197 |
Pagination | 139-153 |
Date Published | 2018 12 |
ISSN | 1521-7035 |
Keywords | Acinetobacter 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 |
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.
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DOI | 10.1016/j.clim.2018.09.008 |
Alternate Journal | Clin Immunol |
PubMed ID | 30240602 |
PubMed Central ID | PMC6289276 |
Grant List | HHSN261200800001C / 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 |