Universität zu Köln

Schiller, Herbert B., Mayr, Christoph H., Leuschner, Gabriela, Strunz, Maximilian, Staab-Weijnitz, Claudia, Preisendoerfer, Stefan, Eckes, Beate, Moinzadeh, Pia, Krieg, Thomas, Schwartz, David A., Hatz, Rudolf A., Behr, Juergen, Mann, Matthias and Eickelberg, Oliver (2017). Deep Proteome Profiling Reveals Common Prevalence of MZB1-Positive Plasma B Cells in Human Lung and Skin Fibrosis. Am. J. Respir. Crit. Care Med., 196 (10). S. 1298 - 1311. NEW YORK: AMER THORACIC SOC. ISSN 1535-4970

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schiller, Herbert B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mayr, Christoph H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Leuschner, Gabriela UNSPECIFIED UNSPECIFIED UNSPECIFIED Strunz, Maximilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Staab-Weijnitz, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Preisendoerfer, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckes, Beate UNSPECIFIED UNSPECIFIED UNSPECIFIED Moinzadeh, Pia UNSPECIFIED UNSPECIFIED UNSPECIFIED Krieg, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwartz, David A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hatz, Rudolf A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Behr, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Mann, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Eickelberg, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-211223
DOI:	10.1164/rccm.201611-2263OC
Journal or Publication Title:	Am. J. Respir. Crit. Care Med.
Volume:	196
Number:	10
Page Range:	S. 1298 - 1311
Date:	2017
Publisher:	AMER THORACIC SOC
Place of Publication:	NEW YORK
ISSN:	1535-4970
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language IDIOPATHIC PULMONARY-FIBROSIS; OLIGOMERIC MATRIX PROTEIN; KEY REGULATOR; TISSUE; MICE; SECRETION; REPAIR; DIFFERENTIATION; IDENTIFICATION; REGENERATION Multiple languages Critical Care Medicine; Respiratory System Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21122