Duodenal inflammation in common variable immunodeficiency has altered transcriptional response to viruses - 03/03/23
Abstract |
Background |
A substantial proportion of common variable immunodeficiency (CVID) patients has duodenal inflammation of largely unknown etiology. However, because of its histologic similarities with celiac disease, gluten sensitivity has been proposed as a potential mechanism.
Objective |
We aimed to elucidate the role of the duodenal microenvironment in the pathogenesis of duodenal inflammation in CVID by investigating the transcriptional, proteomic, and microbial signatures of duodenal biopsy samples in CVID.
Methods |
DNA, total RNA, and protein were isolated from snap-frozen pieces of duodenal biopsy samples from CVID (with and without duodenal inflammation), healthy controls, and patients with celiac disease (untreated). RNA sequencing, mass spectrometry–based proteomics, and 16S ribosomal DNA sequencing (bacteria) were then performed.
Results |
CVID separated from controls in regulation of transcriptional response to lipopolysaccharide and cellular immune responses. These differences were independent of mucosal inflammation. Instead, CVID patients with duodenal inflammation displayed alterations in transcription of genes involved in response to viral infections. Four proteins were differently regulated between CVID patients and healthy controls—DBNL, TRMT11, GCHFR, and IGHA2—independent of duodenal inflammation. Despite similar histology, there were major differences in CVID with duodenal inflammation and celiac disease both at the RNA and protein level. No significant difference was observed in the bacterial gut microbial signature between CVID, celiac, and healthy controls.
Conclusion |
Our findings suggest the existence of altered functions of the duodenal epithelium, particularly in response to lipopolysaccharide and viruses. The latter finding was related to duodenal inflammation, suggesting that viruses, not gluten sensitivity, could be related to duodenal inflammation in CVID.
Le texte complet de cet article est disponible en PDF.Key words : CVID, RNA sequencing, proteomics, microbiome, gut microbiota, microbiota, gastrointestinal tract, duodenum, celiac disease, Primary immunodeficiency, IgA
Abbreviations used : CVID, CVID_all, CVID_IEL, CVID_N, DEG, DEP, GI, GO, IEL, LPS, MS, RNA-Seq, rRNA
Plan
| The first 2 authors contributed equally to this article, and both should be considered first author. |
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| S.F.J. (project 2019089), M.B. (project 2021076), and M.E.M. (project 2012/521) were funded by grants from the South-Eastern Norway Regional Health Authority. In addition, funding from “Anders Jahres fond til vitenskapens fremme” and Unifor Frimed covered various analyses. |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 151 - N° 3
P. 767-777 - mars 2023 Retour au numéro
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