title: Defining immunological dysfunction in sepsis: A requisite tool for precision medicine.
abstract: OBJECTIVE
  Immunological dysregulation is now recognised as a major pathogenic event in sepsis. Stimulation of immune response and immuno-modulation are emerging approaches for the treatment of this disease. Defining the underlying immunological alterations in sepsis is important for the design of future therapies with immuno-modulatory drugs.
  
  
  METHODS
  Clinical studies evaluating the immunological response in adult patients with Sepsis and published in PubMed were reviewed to identify features of immunological dysfunction. For this study we used key words related with innate and adaptive immunity.
  
  
  RESULTS
  Ten major features of immunological dysfunction (FID) were identified involving quantitative and qualitative alterations of [antigen presentation](FID1), [T and B lymphocytes] (FID2), [natural killer cells] (FID3), [relative increase in T regulatory cells] (FID4), [increased expression of PD-1 and PD-ligand1](FID5), [low levels of immunoglobulins](FID6), [low circulating counts of neutrophils and/or increased immature forms in non survivors](FID7), [hyper-cytokinemia] (FID8), [complement consumption] (FID9), [defective bacterial killing by neutrophil extracellular traps](FID10).
  
  
  CONCLUSIONS
  This review article identified ten major features associated with immunosuppression and immunological dysregulation in sepsis. Assessment of these features could help in utilizing precision medicine for the treatment of sepsis with immuno-modulatory drugs.
authors: Infection and Immunity Medical Investigation Unit (IMI), Hospital Clínico Universitario de Valladolid, SACYL/IECSCYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: jfbermejo@saludcastillayleon.es.
authors: Jesús F
authors: JF
authors: Bermejo-Martin
authors: Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, 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: dandaluz@saludcastillayleon.es.
authors: David
authors: D
authors: Andaluz-Ojeda
authors: Infection and Immunity Medical Investigation Unit (IMI), Hospital Clínico Universitario de Valladolid, SACYL/IECSCYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: ralmansa@saludcastillayleon.es.
authors: Raquel
authors: R
authors: Almansa
authors: Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, 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: fgandia@saludcastillayleon.es.
authors: Francisco
authors: F
authors: Gandía
authors: Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Servicio de Anestesiología y Reanimación, Hospital Clínico Universitario de Valladolid, SACYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: jgomez012001@yahoo.es.
authors: Jose Ignacio
authors: JI
authors: Gómez-Herreras
authors: Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Servicio de Anestesiología y Reanimación, Hospital Clínico Universitario de Valladolid, SACYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: esthergzam@hotmail.com.
authors: Esther
authors: E
authors: Gomez-Sanchez
authors: Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Servicio de Anestesiología y Reanimación, Hospital Clínico Universitario de Valladolid, SACYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: maria_her_05@hotmail.com.
authors: María
authors: M
authors: Heredia-Rodríguez
authors: Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: eiros@med.uva.es.
authors: Jose Maria
authors: JM
authors: Eiros
authors: Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada; Sezione di Microbiologia Sperimentale e Clinica, Dipartimento di Scienze Biomediche, Universita' degli Studi di Sassari, Piazza Università, 21, 07100 Sassari SS, Italy; International Institute of Infection and Immunity, Shantou University Medical College, 22 Xinling Road, Shantou, 515041 Guangdong Province, PR China. Electronic address: dkelvin@jidc.org.
authors: David J
authors: DJ
authors: Kelvin
authors: Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Servicio de Anestesiología y Reanimación, Hospital Clínico Universitario de Valladolid, SACYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: eduardo.tamayo@uva.es.
authors: Eduardo
authors: E
authors: Tamayo
mesh_terms: D006801:Humans; D007107:Immune System / Q000503:physiopathology*; D007108:Immune Tolerance; D018805:Sepsis / Q000276:immunology* / Q000473:pathology*
keywords: Antigen presentation; Complement; Dysfunction; Immunoglobulins; Immunological; Neutrophils; PD-1; Sepsis; T/B lymphocytes; Tregs