title: Pulmonary sarcoidosis is associated with exosomal vitamin D-binding protein and inflammatory molecules.
abstract: 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.
  
  
  OBJECTIVE
  We aimed 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
  We performed 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
  More than 690 proteins were identified in the BALF exosomes, several of which displayed significant upregulation in patients, including inflammation-associated proteins, such as leukotriene A4hydrolase. Most of the complement-activating factors were upregulated, whereas the complement regulator CD55 was seen less in patients compared with 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 significantly higher expression in patients.
  
  
  CONCLUSIONS
  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.
authors: Unit for Immunology and Allergy, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors: Maria-Jose
authors: MJ
authors: Martinez-Bravo
authors: Unit for Immunology and Allergy, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors: Casper J E
authors: CJ
authors: Wahlund
authors: Unit for Immunology and Allergy, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors: Khaleda Rahman
authors: KR
authors: Qazi
authors: Turku Centre for Biotechnology, University of Turku, Turku, Finland.
authors: Robert
authors: R
authors: Moulder
authors: Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, University Hospital, Solna, Stockholm, Sweden.
authors: Ana
authors: A
authors: Lukic
authors: Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, University Hospital, Solna, Stockholm, Sweden.
authors: Olof
authors: O
authors: Rådmark
authors: Turku Centre for Biotechnology, University of Turku, Turku, Finland.
authors: Riitta
authors: R
authors: Lahesmaa
authors: Respiratory Unit, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors: Johan
authors: J
authors: Grunewald
authors: Respiratory Unit, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors: Anders
authors: A
authors: Eklund
authors: Unit for Immunology and Allergy, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. Electronic address: Susanne.Gabrielsson@ki.se.
authors: Susanne
authors: S
authors: Gabrielsson
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis* / Q000378:metabolism; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002853:Chromatography, Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D055354:Exosomes / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D017565:Sarcoidosis, Pulmonary / Q000378:metabolism* / Q000473:pathology; D053719:Tandem Mass Spectrometry; D014809:Vitamin D-Binding Protein / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D014809:Vitamin D-Binding Protein
keywords: Exosomes; biomarkers; complement; extracellular vesicles; leukotrienes; proteome; sarcoidosis; vitamin D–binding protein