| Full text | |
| Author(s): Show less - |
Strohmeier, Valentina
;
Andrieux, Geoffroy
;
Unger, Susanne
;
Pascual-Reguant, Anna
;
Klocperk, Adam
;
Seidl, Maximilian
;
Marques, Otavio Cabral
;
Eckert, Marleen
;
Graewe, Katja
;
Shabani, Michelle
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von Spee-Mayer, Caroline
;
Friedmann, David
;
Harder, Ina
;
Gutenberger, Sylvia
;
Keller, Baerbel
;
Proietti, Michele
;
Bulashevska, Alla
;
Grimbacher, Bodo
;
Provaznik, Jan
;
Benes, Vladimir
;
Goldacker, Sigune
;
Schell, Christoph
;
Hauser, Anja E.
;
Boerries, Melanie
;
Hasselblatt, Peter
;
Warnatz, Klaus
Total Authors: 26
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| Document type: | Journal article |
| Source: | JOURNAL OF CLINICAL IMMUNOLOGY; v. 43, n. 2, p. 20-pg., 2022-10-25. |
| Abstract | |
Purpose About 15% of patients with common variable immunodeficiency (CVID) develop a small intestinal enteropathy, which resembles celiac disease with regard to histopathology but evolves from a distinct, poorly defined pathogenesis that has been linked in some cases to chronic norovirus (NV) infection. Interferon-driven inflammation is a prominent feature of CVID enteropathy, but it remains unknown how NV infection may contribute. Methods Duodenal biopsies of CVID patients, stratified according to the presence of villous atrophy (VA), IgA plasma cells (PCs), and chronic NV infection, were investigated by flow cytometry, multi-epitope-ligand cartography, bulk RNAsequencing, and RT-qPCR of genes of interest. Results VA development was connected to the lack of intestinal (IgA(+)) PC, a T helper 1/T helper 17 cell imbalance, and increased recruitment of granzyme (+)CD8(+) T cells and pro-inflammatory macrophages to the affected site. A mixed interferon type VIII and II signature occurred already in the absence of histopathological changes and increased with the severity of the disease and in the absence of (IgA(+)) PCs. Chronic NV infection exacerbated this signature when compared to stagematched NV-negative samples. Conclusions Our study suggests that increased IFN signaling and T-cell cytotoxicity are present already in mild and are aggravated in severe stages (VA) of CVID enteropathy. NV infection preempts local high IFN-driven inflammation, usually only seen in VA, at milder disease stages. Thus, revealing the impact of different drivers of the pathological mixed IFN type VIII and II signature may allow for more targeted treatment strategies in CVID enteropathy and supports the goal of viral elimination. (AU) | |
| FAPESP's process: | 20/01688-0 - Systemic and integrative analysis of the immune response to Zika and Dengue viral infections |
| Grantee: | Otávio Cabral Marques |
| Support Opportunities: | Scholarships in Brazil - Young Researchers |