Deep Proteome Profiling Reveals Common Prevalence of MZB1-positive Plasma B Cells in Human Lung and Skin Fibrosis

Herbert B Schiller; Christoph H Mayr; Gabriela Leuschner; Maximilian Strunz; Claudia Staab-Weijnitz; Stefan Preisendörfer; Beate Eckes; Pia Moinzadeh; Thomas Krieg; David A Schwartz; Rudolf A Hatz; Jürgen Behr; Matthias Mann; Oliver Eickelberg

doi:10.1164/rccm.201611-2263OC

Deep Proteome Profiling Reveals Common Prevalence of MZB1-positive Plasma B Cells in Human Lung and Skin Fibrosis

Herbert B Schiller, Christoph H Mayr, Gabriela Leuschner, Maximilian Strunz, Claudia Staab-Weijnitz, Stefan Preisendörfer, Beate Eckes, Pia Moinzadeh, Thomas Krieg, David A Schwartz, Rudolf A Hatz, Jürgen Behr, Matthias Mann, Oliver Eickelberg

41 Citationer (Scopus)

Abstract

Rationale: Analyzing the molecular heterogeneity of different forms of organ fibrosis may reveal common and specific factors and thus identify potential future therapeutic targets. Objectives: We sought to use proteome-wide profiling of human tissue fibrosis to (1) identify common and specific signatures across end-stage interstitial lung disease (ILD) cases, (2) characterize ILD subgroups in an unbiased fashion, and (3) identify common and specific features of lung and skin fibrosis. Methods: We collected samples of ILD tissue (n = 45) and healthy donor control samples (n = 10), as well as fibrotic skin lesions from localized scleroderma and uninvolved skin (n = 6). Samples were profiled by quantitative label-free mass spectrometry, Western blotting, or confocal imaging. Measurements and Main Results: We determined the abundance of more than 7, 900 proteins and stratified these proteins according to their detergent solubility profiles. Common protein regulations across all ILD cases, as well as distinct ILD subsets, were observed. Proteomic comparison of lung and skin fibrosis identified a common upregulation of marginal zone B- and B1-cell-specific protein (MZB1), the expression of which identified MZB1 /CD38 /CD138 /CD27 /CD45 /CD20 plasma B cells in fibrotic lung and skin tissue. MZB1 levels correlated positively with tissue IgG and negatively with diffusing capacity of the lung for carbon monoxide. Conclusions: Despite the presumably high molecular and cellular heterogeneity of ILD, common protein regulations are observed, even across organ boundaries. The surprisingly high prevalence of MZB1-positive plasma B cells in tissue fibrosis warrants future investigations regarding the causative role of antibody-mediated autoimmunity in idiopathic cases of organ fibrosis, such as idiopathic pulmonary fibrosis.

Originalsprog	Engelsk
Tidsskrift	American Journal of Respiratory and Critical Care Medicine
Vol/bind	196
Udgave nummer	10
Sider (fra-til)	1298–1310
ISSN	1073-449X
DOI	https://doi.org/10.1164/rccm.201611-2263OC
Status	Udgivet - 15 nov. 2017
Udgivet eksternt	Ja

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10.1164/rccm.201611-2263OC

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Schiller, H. B., Mayr, C. H., Leuschner, G., Strunz, M., Staab-Weijnitz, C., Preisendörfer, S., Eckes, B., Moinzadeh, P., Krieg, T., Schwartz, D. A., Hatz, R. A., Behr, J., Mann, M., & Eickelberg, O. (2017). Deep Proteome Profiling Reveals Common Prevalence of MZB1-positive Plasma B Cells in Human Lung and Skin Fibrosis. American Journal of Respiratory and Critical Care Medicine, 196(10), 1298–1310. https://doi.org/10.1164/rccm.201611-2263OC

Deep Proteome Profiling Reveals Common Prevalence of MZB1-positive Plasma B Cells in Human Lung and Skin Fibrosis. / Schiller, Herbert B; Mayr, Christoph H; Leuschner, Gabriela et al.

I: American Journal of Respiratory and Critical Care Medicine, Bind 196, Nr. 10, 15.11.2017, s. 1298–1310.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Schiller, HB, Mayr, CH, Leuschner, G, Strunz, M, Staab-Weijnitz, C, Preisendörfer, S, Eckes, B, Moinzadeh, P, Krieg, T, Schwartz, DA, Hatz, RA, Behr, J, Mann, M & Eickelberg, O 2017, 'Deep Proteome Profiling Reveals Common Prevalence of MZB1-positive Plasma B Cells in Human Lung and Skin Fibrosis', American Journal of Respiratory and Critical Care Medicine, bind 196, nr. 10, s. 1298–1310. https://doi.org/10.1164/rccm.201611-2263OC

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title = "Deep Proteome Profiling Reveals Common Prevalence of MZB1-positive Plasma B Cells in Human Lung and Skin Fibrosis",

abstract = "Rationale: Analyzing the molecular heterogeneity of different forms of organ fibrosis may reveal common and specific factors and thus identify potential future therapeutic targets. Objectives: We sought to use proteome-wide profiling of human tissue fibrosis to (1) identify common and specific signatures across end-stage interstitial lung disease (ILD) cases, (2) characterize ILD subgroups in an unbiased fashion, and (3) identify common and specific features of lung and skin fibrosis. Methods: We collected samples of ILD tissue (n = 45) and healthy donor control samples (n = 10), as well as fibrotic skin lesions from localized scleroderma and uninvolved skin (n = 6). Samples were profiled by quantitative label-free mass spectrometry, Western blotting, or confocal imaging. Measurements and Main Results: We determined the abundance of more than 7, 900 proteins and stratified these proteins according to their detergent solubility profiles. Common protein regulations across all ILD cases, as well as distinct ILD subsets, were observed. Proteomic comparison of lung and skin fibrosis identified a common upregulation of marginal zone B- and B1-cell-specific protein (MZB1), the expression of which identified MZB1 /CD38 /CD138 /CD27 /CD45 /CD20 plasma B cells in fibrotic lung and skin tissue. MZB1 levels correlated positively with tissue IgG and negatively with diffusing capacity of the lung for carbon monoxide. Conclusions: Despite the presumably high molecular and cellular heterogeneity of ILD, common protein regulations are observed, even across organ boundaries. The surprisingly high prevalence of MZB1-positive plasma B cells in tissue fibrosis warrants future investigations regarding the causative role of antibody-mediated autoimmunity in idiopathic cases of organ fibrosis, such as idiopathic pulmonary fibrosis.",

keywords = "Journal Article",

author = "Schiller, {Herbert B} and Mayr, {Christoph H} and Gabriela Leuschner and Maximilian Strunz and Claudia Staab-Weijnitz and Stefan Preisend{\"o}rfer and Beate Eckes and Pia Moinzadeh and Thomas Krieg and Schwartz, {David A} and Hatz, {Rudolf A} and J{\"u}rgen Behr and Matthias Mann and Oliver Eickelberg",

year = "2017",

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doi = "10.1164/rccm.201611-2263OC",

language = "English",

volume = "196",

pages = "1298–1310",

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TY - JOUR

T1 - Deep Proteome Profiling Reveals Common Prevalence of MZB1-positive Plasma B Cells in Human Lung and Skin Fibrosis

AU - Schiller, Herbert B

AU - Mayr, Christoph H

AU - Leuschner, Gabriela

AU - Strunz, Maximilian

AU - Staab-Weijnitz, Claudia

AU - Preisendörfer, Stefan

AU - Eckes, Beate

AU - Moinzadeh, Pia

AU - Krieg, Thomas

AU - Schwartz, David A

AU - Hatz, Rudolf A

AU - Behr, Jürgen

AU - Mann, Matthias

AU - Eickelberg, Oliver

PY - 2017/11/15

Y1 - 2017/11/15

N2 - Rationale: Analyzing the molecular heterogeneity of different forms of organ fibrosis may reveal common and specific factors and thus identify potential future therapeutic targets. Objectives: We sought to use proteome-wide profiling of human tissue fibrosis to (1) identify common and specific signatures across end-stage interstitial lung disease (ILD) cases, (2) characterize ILD subgroups in an unbiased fashion, and (3) identify common and specific features of lung and skin fibrosis. Methods: We collected samples of ILD tissue (n = 45) and healthy donor control samples (n = 10), as well as fibrotic skin lesions from localized scleroderma and uninvolved skin (n = 6). Samples were profiled by quantitative label-free mass spectrometry, Western blotting, or confocal imaging. Measurements and Main Results: We determined the abundance of more than 7, 900 proteins and stratified these proteins according to their detergent solubility profiles. Common protein regulations across all ILD cases, as well as distinct ILD subsets, were observed. Proteomic comparison of lung and skin fibrosis identified a common upregulation of marginal zone B- and B1-cell-specific protein (MZB1), the expression of which identified MZB1 /CD38 /CD138 /CD27 /CD45 /CD20 plasma B cells in fibrotic lung and skin tissue. MZB1 levels correlated positively with tissue IgG and negatively with diffusing capacity of the lung for carbon monoxide. Conclusions: Despite the presumably high molecular and cellular heterogeneity of ILD, common protein regulations are observed, even across organ boundaries. The surprisingly high prevalence of MZB1-positive plasma B cells in tissue fibrosis warrants future investigations regarding the causative role of antibody-mediated autoimmunity in idiopathic cases of organ fibrosis, such as idiopathic pulmonary fibrosis.

AB - Rationale: Analyzing the molecular heterogeneity of different forms of organ fibrosis may reveal common and specific factors and thus identify potential future therapeutic targets. Objectives: We sought to use proteome-wide profiling of human tissue fibrosis to (1) identify common and specific signatures across end-stage interstitial lung disease (ILD) cases, (2) characterize ILD subgroups in an unbiased fashion, and (3) identify common and specific features of lung and skin fibrosis. Methods: We collected samples of ILD tissue (n = 45) and healthy donor control samples (n = 10), as well as fibrotic skin lesions from localized scleroderma and uninvolved skin (n = 6). Samples were profiled by quantitative label-free mass spectrometry, Western blotting, or confocal imaging. Measurements and Main Results: We determined the abundance of more than 7, 900 proteins and stratified these proteins according to their detergent solubility profiles. Common protein regulations across all ILD cases, as well as distinct ILD subsets, were observed. Proteomic comparison of lung and skin fibrosis identified a common upregulation of marginal zone B- and B1-cell-specific protein (MZB1), the expression of which identified MZB1 /CD38 /CD138 /CD27 /CD45 /CD20 plasma B cells in fibrotic lung and skin tissue. MZB1 levels correlated positively with tissue IgG and negatively with diffusing capacity of the lung for carbon monoxide. Conclusions: Despite the presumably high molecular and cellular heterogeneity of ILD, common protein regulations are observed, even across organ boundaries. The surprisingly high prevalence of MZB1-positive plasma B cells in tissue fibrosis warrants future investigations regarding the causative role of antibody-mediated autoimmunity in idiopathic cases of organ fibrosis, such as idiopathic pulmonary fibrosis.

KW - Journal Article

U2 - 10.1164/rccm.201611-2263OC

DO - 10.1164/rccm.201611-2263OC

M3 - Journal article

C2 - 28654764

SN - 1073-449X

VL - 196

SP - 1298

EP - 1310

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

IS - 10

ER -

Deep Proteome Profiling Reveals Common Prevalence of MZB1-positive Plasma B Cells in Human Lung and Skin Fibrosis

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