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Plasma mitochondrial DNA is associated with extrapulmonary sarcoidosis

Authors :
Dylan W. Kelleher
Benjamin C. Reeves
Edward P. Manning
Madeleine Yaggi
Hongyi Pan
Charles S. Dela Cruz
Mridu Gulati
Naftali Kaminski
Taylor Adams
Erica L. Herzog
Changwan Ryu
Anjali Walia
Caitlin Brandsdorfer
Maksym Minasyan
Buqu Hu
Julia Winkler
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.

Details

ISSN :
13993003
Volume :
54
Issue :
2
Database :
OpenAIRE
Journal :
The European respiratory journal
Accession number :
edsair.doi.dedup.....fedc2ca363d41ad02f5b9b33a1840b11