Raquel Almansa1, María Heredia-Rodríguez2, Esther Gomez-Sanchez3, David Andaluz-Ojeda4, Verónica Iglesias5, Lucia Rico6, Alicia Ortega7, Estefanía Gomez-Pesquera8, Pilar Liu9, Marta Aragón10, Jose Maria Eiros11, Maria Ángeles Jiménez-Sousa12, Salvador Resino13, Ignacio Gómez-Herreras14, Jesús F Bermejo-Martín15, Eduardo Tamayo16. 1. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Unidad Apoyo a la Investigación, Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: ralmansa@saludcastillayleon.es. 2. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Servicio de Anestesiología, Hospital Clínico Universitario de Valladolid, SACYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: maria_her_05@hotmail.com. 3. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Servicio de Anestesiología, Hospital Clínico Universitario de Valladolid, SACYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: esthergzam@hotmail.com. 4. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Servicio de Medicina Intensiva, Hospital Clínico Universitario de Valladolid, SACYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: davidandaluz78@yahoo.es. 5. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Unidad Apoyo a la Investigación, Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: viglesiasl@saludcastillayleon.es. 6. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Unidad Apoyo a la Investigación, Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: lrico@saludcastillayleon.es. 7. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Unidad Apoyo a la Investigación, Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: aortegaa@saludcastillayleon.es. 8. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Servicio de Anestesiología, Hospital Clínico Universitario de Valladolid, SACYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: egp29@hotmail.com. 9. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Servicio de Anestesiología, Hospital Clínico Universitario de Valladolid, SACYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: liupili@hotmail.com. 10. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Servicio de Anestesiología, Hospital Clínico Universitario de Valladolid, SACYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: mrt.aragon@gmail.com. 11. Dpto de Microbiología, Universidad de Valladolid, Avenida Ramón y Cajal, 7, 47005 Valladolid, Spain. Electronic address: jmeirosbouza@gmail.com. 12. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología - Instituto de Salud Carlos III, Carretera Majadahonda- Pozuelo km. 2, Majadahonda, 28220 Madrid, Spain. Electronic address: jimenezsousa@yahoo.es. 13. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología - Instituto de Salud Carlos III, Carretera Majadahonda- Pozuelo km. 2, Majadahonda, 28220 Madrid, Spain. Electronic address: salvador.resino@gmail.com. 14. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Servicio de Anestesiología, Hospital Clínico Universitario de Valladolid, SACYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: jgomez012001@yahoo.es. 15. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Unidad Apoyo a la Investigación, Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: jfbermejo@saludcastillayleon.es. 16. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, SACYL/IECSYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Servicio de Anestesiología, Hospital Clínico Universitario de Valladolid, SACYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: tamayo@med.uva.es.
Abstract
OBJECTIVES: Sepsis is characterised by the frequent presence of organ failure and marked immunologic alterations. We studied the association between the extent of organ failure and the transcriptomic response of septic patients. METHODS: Gene expression profiles in the blood of 74 surgical patients with sepsis were compared with those of 30 surgical patients with no sepsis. Differentially expressed genes were assessed for their correlation with the sequential organ failure (SOFA) score. RESULTS: The expression levels of a group of genes participating in the cell cycle (HIST1H1C, CKS2, CCNA2, CDK1, CCNB2, CIT, CCNB1, AURKA, RAD51), neutrophil protease activity (ELANE, ADORA3, MPO, MMP8, CTSG), IL-1R and IL-18R response correlated directly with SOFA and mortality. Genes involved in T cell (LCK, CD3G, CD3D, ZAP70, ICOS, CD3E, CD28, IL2RB, CD8B, CD8A, CD40LG, IL23A, CCL5, SH2D1A, ITK, CD247, TBX21, GATA3, CCR7, LEF1, STAT4) and NK cell immunity (CD244, KLRK1, KLRD1) were inversely associated with SOFA and mortality. CONCLUSIONS: The extent of organ failure in sepsis correlates directly with the existence of imbalanced innate and adaptive responses at the transcriptomic level. Quantification of the expression levels of the genes identified here could contribute to the simultaneous assessment of disease severity and immunological alterations in sepsis.
OBJECTIVES:Sepsis is characterised by the frequent presence of organ failure and marked immunologic alterations. We studied the association between the extent of organ failure and the transcriptomic response of septic patients. METHODS: Gene expression profiles in the blood of 74 surgical patients with sepsis were compared with those of 30 surgical patients with no sepsis. Differentially expressed genes were assessed for their correlation with the sequential organ failure (SOFA) score. RESULTS: The expression levels of a group of genes participating in the cell cycle (HIST1H1C, CKS2, CCNA2, CDK1, CCNB2, CIT, CCNB1, AURKA, RAD51), neutrophil protease activity (ELANE, ADORA3, MPO, MMP8, CTSG), IL-1R and IL-18R response correlated directly with SOFA and mortality. Genes involved in T cell (LCK, CD3G, CD3D, ZAP70, ICOS, CD3E, CD28, IL2RB, CD8B, CD8A, CD40LG, IL23A, CCL5, SH2D1A, ITK, CD247, TBX21, GATA3, CCR7, LEF1, STAT4) and NK cell immunity (CD244, KLRK1, KLRD1) were inversely associated with SOFA and mortality. CONCLUSIONS: The extent of organ failure in sepsis correlates directly with the existence of imbalanced innate and adaptive responses at the transcriptomic level. Quantification of the expression levels of the genes identified here could contribute to the simultaneous assessment of disease severity and immunological alterations in sepsis.
Authors: Timothy E Sweeney; Tej D Azad; Michele Donato; Winston A Haynes; Thanneer M Perumal; Ricardo Henao; Jesús F Bermejo-Martin; Raquel Almansa; Eduardo Tamayo; Judith A Howrylak; Augustine Choi; Grant P Parnell; Benjamin Tang; Marshall Nichols; Christopher W Woods; Geoffrey S Ginsburg; Stephen F Kingsmore; Larsson Omberg; Lara M Mangravite; Hector R Wong; Ephraim L Tsalik; Raymond J Langley; Purvesh Khatri Journal: Crit Care Med Date: 2018-06 Impact factor: 7.598
Authors: Sonia Y Velásquez; Anna Coulibaly; Carsten Sticht; Jutta Schulte; Bianka Hahn; Timo Sturm; Roman Schefzik; Manfred Thiel; Holger A Lindner Journal: Front Immunol Date: 2022-06-30 Impact factor: 8.786
Authors: Michael D Maile; Matthew J Sigakis; Kathleen A Stringer; Elizabeth S Jewell; Milo C Engoren Journal: J Crit Care Date: 2020-01-14 Impact factor: 3.425
Authors: Raquel Almansa; Leonor Nogales; Marta Martín-Fernández; Montse Batlle; Esther Villareal; Lucia Rico; Alicia Ortega; Guillermo López-Campos; David Andaluz-Ojeda; Paula Ramírez; Lorenzo Socias; Luis Tamayo; Jordi Vallés; Jesús F Bermejo-Martín; Ignacio Martín-Loeches Journal: Ann Transl Med Date: 2018-11