Epigenetic Biomarkers for Human Sepsis and Septic Shock: Insights from Immunosuppression

Abstract

Sepsis is a life-threatening condition that occurs when the body responds to an infection damaging its own tissues. Sepsis survivors sometimes suffer from immunosuppression increasing the risk of death. To our best knowledge, there is no ‘gold standard’ for defining immunosuppression except for a composite clinical end point. As the immune system is exposed to epigenetic changes during and after sepsis, research that focuses on identifying new biomarkers to detect septic patients with immunoparalysis could offer new epigenetic-based strategies to predict short- and long-term pathological events related to this life-threatening state. This review describes the most relevant epigenetic mechanisms underlying alterations in the innate and adaptive immune responses described in sepsis and septic shock, and their consequences for immunosuppression states, providing several candidates to become epigenetic biomarkers that could improve sepsis management and help predict immunosuppression in postseptic patients.

Keywords::

• circulating histones
• DNA methylation
• epigenetic biomarkers
• histones PTMs
• immunosuppression
• miRNAs
• PICS
• sepsis
• septic shock

Acknowledgments

J Beltrán thank ISCIII, AES2018 for iPFIS fellowship (IFI18/00015) and Generalitat Valenciana for APOTI fellowship (APOTIP/2017/012). R Osca-Verdegal thank Generalitat Valenciana for APOTI fellowship (APOTIP/2019/31).

Financial & competing interests disclosure

This work was supported by the VLC-Bioclinics grant 2017 and Generalitat Valenciana (GV/2014/132), (GV/2018/127); AES2016 (ISCIII) with grant number PI16/01036 and AES2018 with grant number PI19/0099994 and Proyectos de Desarrollo Tecnológico en Salud with grant number DTS17/132 AES2017, co-financed by the European Regional Development Fund (ERDF), Grand Challenges Canada, Instituto de Salud Carlos III through CIBERer (Biomedical Network Research Center for Rare Diseases and INGENIO2010). The project leading to this results has received funding from “la Caixa” Foundation through CaixaImpulse 2018 programme, under the agreement CI18-0009.

JLG Giménez, C Romá-Mateo and FV Pallardó are inventors of a method with application reference: PCT/EP2016/063935. JLG Giménez is currently the C.E.O. of EpiDisease S.L. EpiDisease is a Spin-Off of the Center for Biomedical Network Research on Rare Diseases (Spanish Institute of Health Instituto de Salud Carlos III), the Biomedical Research Center INCLIVA and the University of Valencia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by the VLC-Bioclinics grant 2017 and Generalitat Valenciana (GV/2014/132), (GV/2018/127); AES2016 (ISCIII) with grant number PI16/01036 and AES2018 with grant number PI19/0099994 and Proyectos de Desarrollo Tecnológico en Salud with grant number DTS17/132 AES2017, co-financed by the European Regional Development Fund (ERDF), Grand Challenges Canada, Instituto de Salud Carlos III through CIBERer (Biomedical Network Research Center for Rare Diseases and INGENIO2010). The project leading to this results has received funding from “la Caixa” Foundation through CaixaImpulse 2018 programme, under the agreement CI18-0009. JLG Giménez, C Romá-Mateo and FV Pallardó are inventors of a method with application reference: PCT/EP2016/063935. JLG Giménez is currently the C.E.O. of EpiDisease S.L. EpiDisease is a Spin-Off of the Center for Biomedical Network Research on Rare Diseases (Spanish Institute of Health Instituto de Salud Carlos III), the Biomedical Research Center INCLIVA and the University of Valencia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.