TY - JOUR
T1 - Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis
AU - the Genetics of Sepsis (GEN-SEP) Network
AU - Hernández-Beeftink, Tamara
AU - Guillen-Guio, Beatriz
AU - Rodríguez-Pérez, Héctor
AU - Marcelino-Rodríguez, Itahisa
AU - Lorenzo-Salazar, Jose M.
AU - Corrales, Almudena
AU - Prieto-González, Miryam
AU - Rodríguez-Pérez, Aurelio
AU - Carriedo, Demetrio
AU - Blanco, Jesús
AU - Ambrós, Alfonso
AU - González-Higueras, Elena
AU - Casanova, Nancy G.
AU - González-Garay, Manuel
AU - Espinosa, Elena
AU - Muriel, Arturo
AU - Domínguez, David
AU - de Lorenzo, Abelardo García
AU - Añón, José M.
AU - Soro, Marina
AU - Belda, Javier
AU - Garcia, Joe G.N.
AU - Villar, Jesús
AU - Flores, Carlos
N1 - Publisher Copyright:
© Copyright © 2021 Hernández-Beeftink, Guillen-Guio, Rodríguez-Pérez, Marcelino-Rodríguez, Lorenzo-Salazar, Corrales, Prieto-González, Rodríguez-Pérez, Carriedo, Blanco, Ambrós, González-Higueras, Casanova, González-Garay, Espinosa, Muriel, Domínguez, de Lorenzo, Añón, Soro, Belda, Garcia, Villar and Flores.
PY - 2021/9/7
Y1 - 2021/9/7
N2 - 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.
AB - 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.
KW - ARDS
KW - DAMPs
KW - mitochondria
KW - mtDNA
KW - survival
KW - whole blood
UR - http://www.scopus.com/inward/record.url?scp=85115388740&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85115388740&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2021.737369
DO - 10.3389/fimmu.2021.737369
M3 - Article
C2 - 34557198
AN - SCOPUS:85115388740
SN - 1664-3224
VL - 12
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 737369
ER -