A1 Refereed original research article in a scientific journal
Pulmonary sarcoidosis is associated with exosomal vitamin D-binding protein and inflammatory molecules
Authors: Maria-Jose Martinez-Bravo, Casper J.E. Wahlund, Khaleda Rahman Qazi, Robert Moulder, Ana Lukic, Olof Rådmark, Riitta Lahesmaa, Johan Grunewald, Anders Eklund, Susanne Gabrielsson
Publisher: Elsevier
Publication year: 2017
Journal: Journal of Allergy and Clinical Immunology
Journal acronym: J Allergy Clin Immunol
Article number: S0091-6749
Volume: 139
Issue: 4
First page : 1186
Last page: 1194
Number of pages: 9
ISSN: 0091-6749
eISSN: 1097-6285
DOI: https://doi.org/10.1016/j.jaci.2016.05.051
Web address : http://www.sciencedirect.com/science/article/pii/S0091674916308508
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/18630613
BACKGROUND: Sarcoidosis is an inflammatory granulomatous disorder characterized by accumulation of TH1-type CD4+T cells and immune effector cells within affected organs, most frequently the lungs. Exosomes are extracellular vesicles conveying intercellular communication with possible diagnostic and therapeutic applications.
OBJECTIVES: Weaimed to provide an understanding of the proinflammatory role of bronchoalveolar lavage fluid (BALF) exosomes in patients with sarcoidosis and to find candidates for disease biomarkers.
METHODS: Weperformed a mass spectrometric proteomics characterization of BALF exosomes from 15 patients with sarcoidosis and 5 healthy control subjects and verified the most interesting results with flow cytometry, ELISA, and Western blot analyses in an additional 39 patients and 22 control subjects.
RESULTS: Morethan 690 proteins were identified in the BALF exosomes, several of which displayed significant upregulation in patients, including inflammation-associated proteins, such as leukotriene A4 hydrolase. Most of the complement-activating factors were upregulated, whereas the complement regulator CD55 was seen less in patients comparedwith healthy control subjects. In addition, for the first time, we detected vitamin D-binding protein in BALF exosomes, which was more abundant in patients. To evaluate exosome-associated vitamin D-binding protein as a biomarker for sarcoidosis, we investigated plasma exosomes from 23 patients and 11 healthy control subjects and found significantlyhigher expression in patients.
CONCLUSION: Together,these data contribute to understanding the role of exosomes in lung disease and provide suggestions for highly warranted sarcoidosis biomarkers. Furthermore, the validation of an exosome-associated biomarker in the blood of patients provides novel, and less invasive, opportunities for disease diagnosis.
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