Plasma mitochondrial DNA is associated with extrapulmonary sarcoidosis.

Autor:	Ryu C; Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Brandsdorfer C; Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Adams T; Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Hu B; Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Kelleher DW; Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Yaggi M; Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Manning EP; Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Walia A; Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Reeves B; Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Pan H; Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Winkler J; Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Minasyan M; Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Dela Cruz CS; Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Kaminski N; Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA., Gulati M; Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.; Equal contribution., Herzog EL; Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA erica.herzog@yale.edu.; Equal contribution.
Jazyk:	angličtina
Zdroj:	The European respiratory journal [Eur Respir J] 2019 Aug 29; Vol. 54 (2). Date of Electronic Publication: 2019 Aug 29 (Print Publication: 2019).
DOI:	10.1183/13993003.01762-2018
Abstrakt:	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 human MT-ATP6 gene in bronchoalveolar (BAL) and plasma samples from healthy controls and patients with sarcoidosis from The Yale Lung Repository; associations between MT-ATP6 concentrations 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-ATP6 concentrations 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 excessive MT-ATP6 concentrations 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. Competing Interests: Conflict of interest: C. Ryu has nothing to disclose. Conflict of interest: C. Brandsdorfer has nothing to disclose. Conflict of interest: T. Adams has nothing to disclose. Conflict of interest: B. Hu has nothing to disclose. Conflict of interest: D.W. Kelleher has nothing to disclose. Conflict of interest: M. Yaggi has nothing to disclose. Conflict of interest: E.P. Manning has nothing to disclose. Conflict of interest: A. Walia has nothing to disclose. Conflict of interest: B. Reeves has nothing to disclose. Conflict of interest: H. Pan has nothing to disclose. Conflict of interest: J. Winkler has nothing to disclose. Conflict of interest: M. Minasyan has nothing to disclose. Conflict of interest: C.S. Dela Cruz has nothing to disclose. Conflict of interest: N. Kaminski has nothing to disclose. Conflict of interest: M. Gulati has nothing to disclose. Conflict of interest: E.L. Herzog has nothing to disclose. (Copyright ©ERS 2019.)
Databáze:	MEDLINE
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