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Am J Respir Crit Care Med. 2017 Nov 15;196(10):1298-1310. doi: 10.1164/rccm.201611-2263OC.

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

Author information

1
1 Comprehensive Pneumology Center, German Research Center for Environmental Health, Munich, Germany.
2
2 German Center for Lung Research (DZL), Germany.
3
3 Department of Internal Medicine V and.
4
4 Department of Dermatology, University of Cologne, Cologne, Germany.
5
5 Division of Respiratory Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Denver, Colorado.
6
6 Center for Thoracic Surgery, Munich Lung Transplant Group, University Hospital Grosshadern, Ludwig-Maximilian University of Munich, Munich, Germany.
7
7 Asklepios Clinics Munich-Gauting, Comprehensive Pneumology Center, Munich, Germany; and.
8
8 Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.

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:

autoimmunity; fibrosis; interstitial lung disease; localized scleroderma (morphea); proteomics

PMID:
28654764
DOI:
10.1164/rccm.201611-2263OC
[Indexed for MEDLINE]

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