Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis

• Published in: Frontiers in immunology Vol. 12; p. 737369
• Main Authors: Hernández-Beeftink, Tamara, Guillen-Guio, Beatriz, Rodríguez-Pérez, Héctor, Marcelino-Rodríguez, Itahisa, Lorenzo-Salazar, Jose M., Corrales, Almudena, Prieto-González, Miryam, Rodríguez-Pérez, Aurelio, Carriedo, Demetrio, Blanco, Jesús, Ambrós, Alfonso, González-Higueras, Elena, Casanova, Nancy G., González-Garay, Manuel, Espinosa, Elena, Muriel, Arturo, Domínguez, David, de Lorenzo, Abelardo García, Añón, José M., Soro, Marina, Belda, Javier, Garcia, Joe G. N., Villar, Jesús, Flores, Carlos
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 07.09.2021
• Subjects: Aged; ARDS; Biomarkers - blood; DAMPs; DNA, Mitochondrial - blood; DNA, Mitochondrial - genetics; Female; Hospital Mortality; Humans; Immunology; Male; Middle Aged; mitochondria; mtDNA; Predictive Value of Tests; Prognosis; Respiratory Distress Syndrome - blood; Respiratory Distress Syndrome - diagnosis; Respiratory Distress Syndrome - genetics; Respiratory Distress Syndrome - mortality; Risk Assessment; Risk Factors; Sepsis - blood; Sepsis - diagnosis; Sepsis - genetics; Sepsis - mortality; Spain; survival; Time Factors; whole blood; Spain; whole blood; mtDNA; mitochondria; ARDS; survival; DAMPs
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.737369

Acute respiratory distress syndrome (ARDS) is an inflammatory process of the lungs that develops primarily in response to pulmonary or systemic sepsis, resulting in a disproportionate death toll in intensive care units (ICUs). Given its role as a critical activator of the inflammatory and innate immune responses, previous studies have reported that an increase of circulating cell-free mitochondrial DNA (mtDNA) is a biomarker for fatal outcome in the ICU. Here we analyzed the association of whole-blood mtDNA (wb-mtDNA) copies with 28-day survival from sepsis and sepsis-associated ARDS. We analyzed mtDNA data from 687 peripheral whole-blood samples within 24 h of sepsis diagnosis from unrelated Spanish patients with sepsis (264 with ARDS) included in the GEN-SEP study. The wb-mtDNA copies were obtained from the array intensities of selected probes, with 100% identity with mtDNA and with the largest number of mismatches with the nuclear sequences, and normalized across the individual-probe intensities. We used Cox regression models for testing the association with 28-day survival. We observed that wb-mtDNA copies were significantly associated with 28-day survival in ARDS patients (hazard ratio = 3.65, 95% confidence interval = 1.39–9.59, p = 0.009) but not in non-ARDS patients. Our findings support that wb-mtDNA copies at sepsis diagnosis could be considered an early prognostic biomarker in sepsis-associated ARDS patients. Future studies will be needed to evaluate the mechanistic links of this observation with the pathogenesis of ARDS.