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Plasma mitochondrial DNA is associated with extrapulmonary sarcoidosis
- Source :
- Eur Respir J
- Publication Year :
- 2019
-
Abstract
- Sarcoidosis is an unpredictable granulomatous disease in which African Americans disproportionately experience aggressive phenotypes. Mitochondrial DNA (mtDNA) released by cells in response to various stressors contributes to tissue remodelling and inflammation. While extracellular mtDNA has emerged as a biomarker in multiple diseases, its relevance to sarcoidosis remains unknown. We aimed to define an association between extracellular mtDNA and clinical features of sarcoidosis.Extracellular mtDNA concentrations were measured using quantitative PCR for the humanMT-ATP6gene in bronchoalveolar (BAL) and plasma samples from healthy controls and patients with sarcoidosis from The Yale Lung Repository; associations betweenMT-ATP6concentrations and Scadding stage, extrapulmonary disease and demographics were sought. Results were validated in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis cohort.Relative to controls,MT-ATP6concentrations in sarcoidosis subjects were robustly elevated in the BAL fluid and plasma, particularly in the plasma of patients with extrapulmonary disease. Relative to Caucasians, African Americans displayed excessiveMT-ATP6concentrations in the BAL fluid and plasma, for which the latter compartment correlated with significantly higher odds of extrapulmonary disease.Enrichments in extracellular mtDNA in sarcoidosis are associated with extrapulmonary disease and African American descent. Further study into the mechanistic basis of these clinical findings may lead to novel pathophysiologic and therapeutic insights.
- Subjects :
- 0301 basic medicine
Pulmonary and Respiratory Medicine
Adult
Male
Mitochondrial DNA
Inflammation
Disease
Bronchoalveolar Lavage
DNA, Mitochondrial
Article
03 medical and health sciences
0302 clinical medicine
Sarcoidosis, Pulmonary
medicine
Humans
HMGB1 Protein
Lung
Aged
medicine.diagnostic_test
business.industry
Case-control study
Middle Aged
Mitochondrial Proton-Translocating ATPases
medicine.disease
030104 developmental biology
Bronchoalveolar lavage
medicine.anatomical_structure
HEK293 Cells
Phenotype
030228 respiratory system
Case-Control Studies
Toll-Like Receptor 9
Immunology
Biomarker (medicine)
Female
Sarcoidosis
medicine.symptom
business
Bronchoalveolar Lavage Fluid
Biomarkers
Subjects
Details
- ISSN :
- 13993003
- Volume :
- 54
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- The European respiratory journal
- Accession number :
- edsair.doi.dedup.....fedc2ca363d41ad02f5b9b33a1840b11