• Something wrong with this record ?

Interferon-Driven Immune Dysregulation in Common Variable Immunodeficiency-Associated Villous Atrophy and Norovirus Infection

V. Strohmeier, G. Andrieux, S. Unger, A. Pascual-Reguant, A. Klocperk, M. Seidl, OC. Marques, M. Eckert, K. Gräwe, M. Shabani, C. von Spee-Mayer, D. Friedmann, I. Harder, S. Gutenberger, B. Keller, M. Proietti, A. Bulashevska, B. Grimbacher, J....

. 2023 ; 43 (2) : 371-390. [pub] 20221025

Language English Country Netherlands

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc23004419

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 RNA-sequencing, 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 I/III 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 stage-matched 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 I/III and II signature may allow for more targeted treatment strategies in CVID enteropathy and supports the goal of viral elimination.

Center for Chronic Immunodeficiency Medical Center University of Freiburg Faculty of Medicine University of Freiburg Freiburg Germany

CIBSS Centre for Integrative Biological Signalling Studies Albert Ludwigs University Freiburg Germany

Department of Clinical and Toxicological Analyses School of Pharmaceutical Sciences University of São Paulo São Paulo SP Brazil

Department of Immunology 2Nd Faculty of Medicine Charles University and University Hospital in Motol Prague Czech Republic

Department of Immunology Institute of Biomedical Sciences University of São Paulo São Paulo SP Brazil

Department of Medicine 2 Medical Center University of Freiburg Faculty of Medicine University of Freiburg Freiburg Germany

Department of Pharmacy and Postgraduate Program of Health and Science Federal University of Rio Grande do Norte Natal Brazil

Department of Rheumatology and Clinical Immunology Charité Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt Universität Zu Berlin Charitéplatz 1 10117 Berlin Germany

Department of Rheumatology and Clinical Immunology Medical Center University of Freiburg Faculty of Medicine University of Freiburg Freiburg Germany

DZIF German Center for Infection Research Satellite Center Freiburg Freiburg Germany

European Molecular Biology Laboratory Genomics Core Facility Heidelberg Germany

Faculty of Biology University of Freiburg Freiburg Germany

German Cancer Consortium Partner Site Freiburg 79110 Freiburg Germany

Immune Dynamics Deutsches Rheuma Forschungszentrum a Leibniz Institute Charitéplatz 1 10117 Berlin Germany

Institute for Surgical Pathology University Medical Center Freiburg Freiburg Germany

Institute of Medical Bioinformatics and Systems Medicine Medical Center University of Freiburg Faculty of Medicine University of Freiburg Freiburg Germany

Institute of Pathology Heinrich Heine University and University Hospital of Dusseldorf Dusseldorf Germany

Network of Immunity in Infection Malignancy and Autoimmunity São Paulo SP Brazil

RESIST Cluster of Excellence 2155 to Hanover Medical School Satellite Center Freiburg Freiburg Germany

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc23004419
003      
CZ-PrNML
005      
20230425141350.0
007      
ta
008      
230418s2023 ne f 000 0|eng||
009      
AR
024    7_
$a 10.1007/s10875-022-01379-2 $2 doi
035    __
$a (PubMed)36282455
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a ne
100    1_
$a Strohmeier, Valentina $u Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Faculty of Biology, University of Freiburg, Freiburg, Germany
245    10
$a Interferon-Driven Immune Dysregulation in Common Variable Immunodeficiency-Associated Villous Atrophy and Norovirus Infection / $c V. Strohmeier, G. Andrieux, S. Unger, A. Pascual-Reguant, A. Klocperk, M. Seidl, OC. Marques, M. Eckert, K. Gräwe, M. Shabani, C. von Spee-Mayer, D. Friedmann, I. Harder, S. Gutenberger, B. Keller, M. Proietti, A. Bulashevska, B. Grimbacher, J. Provaznik, V. Benes, S. Goldacker, C. Schell, AE. Hauser, M. Boerries, P. Hasselblatt, K. Warnatz
520    9_
$a 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 RNA-sequencing, 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 I/III 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 stage-matched 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 I/III and II signature may allow for more targeted treatment strategies in CVID enteropathy and supports the goal of viral elimination.
650    _2
$a lidé $7 D006801
650    _2
$a atrofie $x komplikace $x patologie $7 D001284
650    12
$a infekce viry z čeledi Caliciviridae $x imunologie $7 D017250
650    _2
$a CD8-pozitivní T-lymfocyty $7 D018414
650    12
$a běžná variabilní imunodeficience $x komplikace $x imunologie $7 D017074
650    _2
$a imunoglobulin A $7 D007070
650    _2
$a zánět $x komplikace $7 D007249
650    _2
$a interferony $7 D007372
650    12
$a Norovirus $x fyziologie $7 D029322
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Andrieux, Geoffroy $u Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
700    1_
$a Unger, Susanne $u Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
700    1_
$a Pascual-Reguant, Anna $u Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Charitéplatz 1, 10117, Berlin, Germany $u Immune Dynamics, Deutsches Rheuma-Forschungszentrum (DRFZ), a Leibniz Institute, Charitéplatz 1, 10117, Berlin, Germany
700    1_
$a Klocperk, Adam $u Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Department of Immunology, 2Nd Faculty of Medicine, Charles University and University Hospital in Motol, Prague, Czech Republic
700    1_
$a Seidl, Maximilian $u Institute for Surgical Pathology, University Medical Center Freiburg, Freiburg, Germany $u Institute of Pathology, Heinrich Heine University and University Hospital of Dusseldorf, Dusseldorf, Germany
700    1_
$a Marques, Otavio Cabral $u Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil $u Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil $u Network of Immunity in Infection, Malignancy, and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), São Paulo, SP, Brazil $u Department of Pharmacy and Postgraduate Program of Health and Science, Federal University of Rio Grande do Norte, Natal, Brazil
700    1_
$a Eckert, Marleen $u Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Faculty of Biology, University of Freiburg, Freiburg, Germany
700    1_
$a Gräwe, Katja $u Institute for Surgical Pathology, University Medical Center Freiburg, Freiburg, Germany
700    1_
$a Shabani, Michelle $u Institute for Surgical Pathology, University Medical Center Freiburg, Freiburg, Germany
700    1_
$a von Spee-Mayer, Caroline $u Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
700    1_
$a Friedmann, David $u Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Faculty of Biology, University of Freiburg, Freiburg, Germany
700    1_
$a Harder, Ina $u Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
700    1_
$a Gutenberger, Sylvia $u Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
700    1_
$a Keller, Baerbel $u Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
700    1_
$a Proietti, Michele $u Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u RESIST - Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg, Freiburg, Germany
700    1_
$a Bulashevska, Alla $u Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
700    1_
$a Grimbacher, Bodo $u Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u RESIST - Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg, Freiburg, Germany $u DZIF - German Center for Infection Research, Satellite Center Freiburg, Freiburg, Germany $u CIBSS - Centre for Integrative Biological Signalling Studies, Albert-Ludwigs University, Freiburg, Germany
700    1_
$a Provaznik, Jan $u European Molecular Biology Laboratory (EMBL), Genomics Core Facility, Heidelberg, Germany
700    1_
$a Benes, Vladimir $u European Molecular Biology Laboratory (EMBL), Genomics Core Facility, Heidelberg, Germany
700    1_
$a Goldacker, Sigune $u Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
700    1_
$a Schell, Christoph $u Institute for Surgical Pathology, University Medical Center Freiburg, Freiburg, Germany
700    1_
$a Hauser, Anja E $u Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Charitéplatz 1, 10117, Berlin, Germany $u Immune Dynamics, Deutsches Rheuma-Forschungszentrum (DRFZ), a Leibniz Institute, Charitéplatz 1, 10117, Berlin, Germany
700    1_
$a Boerries, Melanie $u Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany $u German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site Freiburg, 79110, Freiburg, Germany
700    1_
$a Hasselblatt, Peter $u Department of Medicine II, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
700    1_
$a Warnatz, Klaus $u Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. klaus.warnatz@uniklinik-freiburg.de $u Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. klaus.warnatz@uniklinik-freiburg.de $1 https://orcid.org/000000021172865X
773    0_
$w MED00002589 $t Journal of clinical immunology $x 1573-2592 $g Roč. 43, č. 2 (2023), s. 371-390
856    41
$u https://pubmed.ncbi.nlm.nih.gov/36282455 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20230418 $b ABA008
991    __
$a 20230425141347 $b ABA008
999    __
$a ok $b bmc $g 1924853 $s 1190628
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2023 $b 43 $c 2 $d 371-390 $e 20221025 $i 1573-2592 $m Journal of clinical immunology $n J Clin Immunol $x MED00002589
LZP    __
$a Pubmed-20230418

Find record

Citation metrics

Archiving options