Skip to main content

ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Molecular Bacterial Pathogenesis
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1532417

Epigenome-wide DNA methylation profiling in septic and non-septic patients with similar infections: Potential use as sepsis biomarkers

Provisionally accepted
Ian López-Cruz Ian López-Cruz 1,2*Jose Luis García-Giménez Jose Luis García-Giménez 2,3,4*Manuel Madrazo Manuel Madrazo 1,2Judit Garcia Judit Garcia 5Laura Piles Laura Piles 1Federico V Pallardó Federico V Pallardó 2,3,4Arturo Artero Arturo Artero 1,2
  • 1 Doctor Peset University Hospital, Valencia, Spain
  • 2 Faculty of Medicine and Dentistry, University of Valencia, València, Valencian Community, Spain
  • 3 INCLIVA Biomedical Research Institute, Valencia, Spain
  • 4 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Madrid Community, Spain
  • 5 EpiDisease S.L., Valencia, Spain

The final, formatted version of the article will be published soon.

    Sepsis is a life-threatening condition caused by a dysregulated immune response to infection, leading to organ failure. Despite its significant global burden, the underlying mechanisms of immune dysfunction in sepsis remain incompletely understood.This study explores the role of DNA methylation in white blood cells in sepsis pathogenesis by assessing a prospective case-control study comparing DNA methylation profiles between patients with community-acquired sepsis and matched controls with similar infections who did not develop sepsis.By analyzing whole blood samples from patients with community-acquired infections, we identified significant differential DNA methylation patterns between septic and non-septic individuals. Our results suggest that DNA methylation changes are closely linked to the pathophysiological processes of sepsis, influencing immune cell activation, inflammation, and organ dysfunction.The most prominent findings include the hypomethylation of immune-related genes (SERPINA1, AZU1, MPO, and SLX4), which were strongly correlated with clinical severity and inflammatory markers such as SOFA scores and PCT levels.Correlation analyses demonstrated significant associations between the methylation levels of these genes and clinical severity markers, such as SOFA score and PCT levels. Notably, SLX4 hypomethylation showed the highest predictive value for poor prognosis (AUC 0.821), while SERPINA1 hypomethylation exhibited strong diagnostic potential for sepsis (AUC 0.858).Our findings underscore the potential of DNA methylation changes, particularly in immune-related genes, to enhance the early detection of sepsis and to stratify patients based on severity. Future research should explore the therapeutic implications of these epigenetic alterations in sepsis care.

    Keywords: Sepsis, septic shock, DNA Methylation, epigenetics, biomarkers, Inflammation, Immune System

    Received: 21 Nov 2024; Accepted: 31 Dec 2024.

    Copyright: © 2024 López-Cruz, García-Giménez, Madrazo, Garcia, Piles, Pallardó and Artero. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Ian López-Cruz, Doctor Peset University Hospital, Valencia, Spain
    Jose Luis García-Giménez, Faculty of Medicine and Dentistry, University of Valencia, València, 46010, Valencian Community, Spain

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.