Molecular signatures of a disturbed nasal barrier function in the primary tissue of Wegener's granulomatosis

M. Laudien; R. Häsler; J. Wohlers; J. Böck; S. Lipinski; L. Bremer; R. Podschun; P. Ambrosch; P. Lamprecht; P. Rosenstiel; A. Till

doi:10.1038/mi.2011.9

Molecular signatures of a disturbed nasal barrier function in the primary tissue of Wegener's granulomatosis

M. Laudien^*, R. Häsler, J. Wohlers, J. Böck, S. Lipinski, L. Bremer, R. Podschun, P. Ambrosch, P. Lamprecht, P. Rosenstiel, A. Till

^*Corresponding author for this work

Department of Rheumatology and Clinical Immunology

University of Kiel

27 Citations (Scopus)

Abstract

Wegener's granulomatosis (WG) is a complex autoimmune disease of unknown etiology, frequently involving localized inflammation of the nasal mucosa as an early manifestation. The current hypothesis suggests that the disease is triggered by a disturbed interaction between genetic and environmental effects, such as an altered microflora at mucosal layers. In this study, a systematic assessment of 49 transcripts with potential pathophysiological relevance was performed using quantitative real-time PCR in nasal mucosa samples of more than 80 individuals, including normal control (NC) individuals and disease controls. In addition, colonization with Staphylococcus aureus was quantified in the same individuals to assess its impact on transcriptomic signatures. Transcription profiles show an increased heterogeneity in diseased individuals. In all, 10 transcripts were identified to be differentially expressed (P0.05, false discovery rate 0.05) between patients with WG and NC individuals. These transcripts include antimicrobial peptides (human Β-defensin (DEFB)1: fold-change WG vs. controls: 4.45, lysozyme: 3.4, DEFB4 and S100A7 (S100 calcium-binding protein A7): both switched on in WG), innate immune receptors (Toll-like receptor 4: 2.1, NOD-like receptor C3: 2.1, scavenger receptor CD36: 2.9), and cytokines (interferon-γ: 14, transforming growth factor-Β 1: 1.4, interleukin-17D: 2.7). These transcriptional profiles are independent of S. aureus colonization. This study for the first time describes that, on the basis of data obtained from the primary nasal tissue, WG exhibits molecular features that allow its differentiation from other inflammatory disorders with involvement of the nasal mucosa. Further studies based on these findings may enable the identification of subphenotypes, which are currently discussed as an important target for a personalized medicine approach, aiming to reduce side effects and the number of therapy non-responders.

Original language	English
Journal	Mucosal Immunology
Volume	4
Issue number	5
Pages (from-to)	564-573
Number of pages	10
ISSN	1933-0219
DOIs	https://doi.org/10.1038/mi.2011.9
Publication status	Published - 01.09.2011

Funding

We thank R Gl ä ser and H Lange for valuable reagents. A H ö lzgen, U Kreutz, D Oelsner, T Kaacksteen, M Schlapkohl, A Graeff, T G ö r ö gh, and A-M R ö en are gratefully acknowledged for their expert technical assistance. We deeply acknowledge the participation of all patients and healthy volunteers who took part in this study. This work was supported by grants from the German Research Foundation (DFG) funded Clinical Research Unit / KFO 170, the Excellence Cluster “ Inflammation at Interfaces, ” and the National Genome Research Network (NGFN plus).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/mi.2011.9

Cite this

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title = "Molecular signatures of a disturbed nasal barrier function in the primary tissue of Wegener's granulomatosis",

abstract = "Wegener's granulomatosis (WG) is a complex autoimmune disease of unknown etiology, frequently involving localized inflammation of the nasal mucosa as an early manifestation. The current hypothesis suggests that the disease is triggered by a disturbed interaction between genetic and environmental effects, such as an altered microflora at mucosal layers. In this study, a systematic assessment of 49 transcripts with potential pathophysiological relevance was performed using quantitative real-time PCR in nasal mucosa samples of more than 80 individuals, including normal control (NC) individuals and disease controls. In addition, colonization with Staphylococcus aureus was quantified in the same individuals to assess its impact on transcriptomic signatures. Transcription profiles show an increased heterogeneity in diseased individuals. In all, 10 transcripts were identified to be differentially expressed (P0.05, false discovery rate 0.05) between patients with WG and NC individuals. These transcripts include antimicrobial peptides (human Β-defensin (DEFB)1: fold-change WG vs. controls: 4.45, lysozyme: 3.4, DEFB4 and S100A7 (S100 calcium-binding protein A7): both switched on in WG), innate immune receptors (Toll-like receptor 4: 2.1, NOD-like receptor C3: 2.1, scavenger receptor CD36: 2.9), and cytokines (interferon-γ: 14, transforming growth factor-Β 1: 1.4, interleukin-17D: 2.7). These transcriptional profiles are independent of S. aureus colonization. This study for the first time describes that, on the basis of data obtained from the primary nasal tissue, WG exhibits molecular features that allow its differentiation from other inflammatory disorders with involvement of the nasal mucosa. Further studies based on these findings may enable the identification of subphenotypes, which are currently discussed as an important target for a personalized medicine approach, aiming to reduce side effects and the number of therapy non-responders.",

author = "M. Laudien and R. H{\"a}sler and J. Wohlers and J. B{\"o}ck and S. Lipinski and L. Bremer and R. Podschun and P. Ambrosch and P. Lamprecht and P. Rosenstiel and A. Till",

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T1 - Molecular signatures of a disturbed nasal barrier function in the primary tissue of Wegener's granulomatosis

AU - Laudien, M.

AU - Häsler, R.

AU - Wohlers, J.

AU - Böck, J.

AU - Lipinski, S.

AU - Bremer, L.

AU - Podschun, R.

AU - Ambrosch, P.

AU - Lamprecht, P.

AU - Rosenstiel, P.

AU - Till, A.

PY - 2011/9/1

Y1 - 2011/9/1

N2 - Wegener's granulomatosis (WG) is a complex autoimmune disease of unknown etiology, frequently involving localized inflammation of the nasal mucosa as an early manifestation. The current hypothesis suggests that the disease is triggered by a disturbed interaction between genetic and environmental effects, such as an altered microflora at mucosal layers. In this study, a systematic assessment of 49 transcripts with potential pathophysiological relevance was performed using quantitative real-time PCR in nasal mucosa samples of more than 80 individuals, including normal control (NC) individuals and disease controls. In addition, colonization with Staphylococcus aureus was quantified in the same individuals to assess its impact on transcriptomic signatures. Transcription profiles show an increased heterogeneity in diseased individuals. In all, 10 transcripts were identified to be differentially expressed (P0.05, false discovery rate 0.05) between patients with WG and NC individuals. These transcripts include antimicrobial peptides (human Β-defensin (DEFB)1: fold-change WG vs. controls: 4.45, lysozyme: 3.4, DEFB4 and S100A7 (S100 calcium-binding protein A7): both switched on in WG), innate immune receptors (Toll-like receptor 4: 2.1, NOD-like receptor C3: 2.1, scavenger receptor CD36: 2.9), and cytokines (interferon-γ: 14, transforming growth factor-Β 1: 1.4, interleukin-17D: 2.7). These transcriptional profiles are independent of S. aureus colonization. This study for the first time describes that, on the basis of data obtained from the primary nasal tissue, WG exhibits molecular features that allow its differentiation from other inflammatory disorders with involvement of the nasal mucosa. Further studies based on these findings may enable the identification of subphenotypes, which are currently discussed as an important target for a personalized medicine approach, aiming to reduce side effects and the number of therapy non-responders.

AB - Wegener's granulomatosis (WG) is a complex autoimmune disease of unknown etiology, frequently involving localized inflammation of the nasal mucosa as an early manifestation. The current hypothesis suggests that the disease is triggered by a disturbed interaction between genetic and environmental effects, such as an altered microflora at mucosal layers. In this study, a systematic assessment of 49 transcripts with potential pathophysiological relevance was performed using quantitative real-time PCR in nasal mucosa samples of more than 80 individuals, including normal control (NC) individuals and disease controls. In addition, colonization with Staphylococcus aureus was quantified in the same individuals to assess its impact on transcriptomic signatures. Transcription profiles show an increased heterogeneity in diseased individuals. In all, 10 transcripts were identified to be differentially expressed (P0.05, false discovery rate 0.05) between patients with WG and NC individuals. These transcripts include antimicrobial peptides (human Β-defensin (DEFB)1: fold-change WG vs. controls: 4.45, lysozyme: 3.4, DEFB4 and S100A7 (S100 calcium-binding protein A7): both switched on in WG), innate immune receptors (Toll-like receptor 4: 2.1, NOD-like receptor C3: 2.1, scavenger receptor CD36: 2.9), and cytokines (interferon-γ: 14, transforming growth factor-Β 1: 1.4, interleukin-17D: 2.7). These transcriptional profiles are independent of S. aureus colonization. This study for the first time describes that, on the basis of data obtained from the primary nasal tissue, WG exhibits molecular features that allow its differentiation from other inflammatory disorders with involvement of the nasal mucosa. Further studies based on these findings may enable the identification of subphenotypes, which are currently discussed as an important target for a personalized medicine approach, aiming to reduce side effects and the number of therapy non-responders.

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DO - 10.1038/mi.2011.9

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SN - 1933-0219

VL - 4

SP - 564

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JO - Mucosal Immunology

JF - Mucosal Immunology

IS - 5

ER -

Molecular signatures of a disturbed nasal barrier function in the primary tissue of Wegener's granulomatosis

Abstract

Funding

UN SDGs

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Other files and links

Fingerprint

CRU 170: Early Pathogenesis of Wegener's Granulomatosis: From Innate Immunity with Granuloma Formation to Autoimmunity.

Cite this

Molecular signatures of a disturbed nasal barrier function in the primary tissue of Wegener's granulomatosis

Abstract

Funding

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

CRU 170: Early Pathogenesis of Wegener's Granulomatosis: From Innate Immunity with Granuloma Formation to Autoimmunity.

Cite this