AUTHOR=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 TITLE=Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.737369 DOI=10.3389/fimmu.2021.737369 ISSN=1664-3224 ABSTRACT=

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.