CVID enteropathy is characterized by exceeding low mucosal IgA levels and interferon-driven inflammation possibly related to the presence of a pathobiont

Shulzhenko, Natalia; Dong, Xiaoxi; Vyshenska, Dariia; Greer, Renee L.; Gurung, Manoj; Vasquez-Perez, Stephany; Peremyslova, Ekaterina; Sosnovtsev, Stanislav; Quezado, Martha; Yao, Michael; Montgomery-Recht, Kim; Strober, Warren; Fuss, Ivan J.; Morgun, Andrey

doi:10.1016/j.clim.2018.09.008

Title: CVID enteropathy is characterized by exceeding low mucosal IgA levels and interferon-driven inflammation possibly related to the presence of a pathobiont

Journal Article · 30 November 2018 · Clinical Immunology

DOI: https://doi.org/10.1016/j.clim.2018.09.008 · OSTI ID:1580862

Shulzhenko, Natalia ^[1]; Dong, Xiaoxi ^[1]; Vyshenska, Dariia ^[1]; Greer, Renee L. ^[1];

^[1]; Vasquez-Perez, Stephany ^[1]; Peremyslova, Ekaterina ^[1]; Sosnovtsev, Stanislav ^[2]; Quezado, Martha ^[2]; Yao, Michael ^[3]; Montgomery-Recht, Kim ^[3]; Strober, Warren ^[2]; Fuss, Ivan J. ^[2]; Morgun, Andrey ^[1]

Oregon State Univ., Corvallis, OR (United States)
National Inst. of Health (NIH), Bethesda, MD (United States)
National Inst. of Health (NIH), Bethesda, MD (United States); Washington DC VA Medical Center, Washington DC (United States)

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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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1580862

Journal Information:: Clinical Immunology, Journal Name: Clinical Immunology Journal Issue: C Vol. 197; ISSN 1521-6616

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Primary Humoral Immune Deficiencies: Overlooked Mimickers of Chronic Immune-Mediated Gastrointestinal Diseases in Adults Malesza, Ida Judyta; Malesza, Michał; Krela-Kaźmierczak, Iwona International Journal of Molecular Sciences, Vol. 21, Issue 15 https://doi.org/10.3390/ijms21155223	journal	July 2020
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