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

Frontiers in Immunology

Alfonso Ambrós¹  Elena González-Higueras²  Joe G. N. Garcia³  Nancy G. Casanova³  Manuel González-Garay⁴  David Domínguez⁵  Elena Espinosa⁵  Abelardo García de Lorenzo⁶  José M. Añón⁶  Marina Soro⁷  Javier Belda⁷  Jesús Villar⁸  Almudena Corrales⁸  Carlos Flores⁸  Aurelio Rodríguez-Pérez^1,10  Jose M. Lorenzo-Salazar^1,11  Miryam Prieto-González^1,12  Demetrio Carriedo^1,13  Jesús Blanco^1,14  Arturo Muriel^1,14  Tamara Hernández-Beeftink^1,15  Itahisa Marcelino-Rodríguez^1,16  Beatriz Guillen-Guio^1,16  Héctor Rodríguez-Pérez^1,16 

[1] 0Intensive Care Unit, Hospital General de Ciudad Real, Ciudad Real, Spain;1Intensive Care Unit, Hospital Virgen de la Luz, Cuenca, Spain;2Department of Medicine, The University of Arizona, Tucson, AZ, United States;3SPECTRUM, LLC, Phoenix, AZ, United States;4Department of Anesthesiology, Hospital Universitario N.S. de Candelaria, Santa Cruz de Tenerife, Spain;5Intensive Care Unit, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain;6Anesthesiology and Critical Care Department, Hospital Clinico Universitario of Valencia, Valencia, Spain;CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain;Department of Anesthesiology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain;Department of Medical and Surgical Sciences, University of Las Palmas de Gran Canaria, Gran Canaria, Spain;Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Tenerife, Spain;Intensive Care Unit, Complejo Asistencial Universitario de Palencia, Palencia, Spain;Intensive Care Unit, Complejo Hospitalario Universitario de León, León, Spain;Intensive Care Unit, Hospital Universitario Rio Hortega, Valladolid, Spain;Research Unit, Hospital Universitario Dr. Negrin, Las Palmas de Gran Canaria, Spain;Research Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, Santa Cruz de Tenerife, Spain;

关键词: ARDS;    mitochondria;    DAMPs;    whole blood;    mtDNA;    survival;   

DOI  :  10.3389/fimmu.2021.737369

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown