title: Genetic polymorphisms of innate and adaptive immunity as predictors of outcome in critically ill patients.
abstract: Sepsis and septic shock frequently cause the admission or complicate the clinical course of critically ill patients admitted in the intensive care units (ICU). Genetic variations disrupting the immune sensing of infectious organisms, could affect the ability of the immune system to respond to infection, and may influence both the genetic predisposition to infection and the diversity of the clinical presentation of sepsis. The aim of this study was to uncover possible associations between common functional immune gene polymorphisms (of both innate and adaptive immunity) and ICU-acquired sepsis and mortality. The TLR4-D299G (rs4986790), TLR4-T399I (rs4986791), C2-c.841_849+19del28 (rs9332736), TACI-C104R (rs34557412), BAFFR-P21R (rs77874543), and BAFFR-H159Y (rs61756766) polymorphisms were detected in a cohort of 215 critically ill patients, admitted in an 8-bed medical/surgical ICU. Interestingly, TLR4-D299G, TLR4-T399I and BAFFR-P21R carriage was associated with a lower risk of ICU-acquired sepsis. This association applied particularly in medical patients, while in trauma and surgical patients no significant associations were observed. Moreover, carriers of TACI-C104R displayed an undiagnosed mild to moderate hypogammaglobulinemia along with a significantly lower survival rate in the ICU, although lethal events were not attributed to sepsis. These findings further elucidate the role that host immune genetic variations may play in the susceptibility to ICU-acquired sepsis and ICU mortality.
authors.affiliation: Intensive Care Unit, Thriassion General Hospital of Eleusis, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Kompoti
authors.affiliation: Department of Immunology and Histocompatibility, University of Thessaly, School of Health Sciences, Faculty of Medicine, Larissa, Greece.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Michopoulos
authors.affiliation: Intensive Care Unit, Thriassion General Hospital of Eleusis, Athens, Greece.
authors.forename: Martha
authors.initials: M
authors.lastname: Michalia
authors.affiliation: Intensive Care Unit, Thriassion General Hospital of Eleusis, Athens, Greece.
authors.forename: Phyllis-Maria
authors.initials: PM
authors.lastname: Clouva-Molyvdas
authors.affiliation: Department of Immunology and Histocompatibility, University of Thessaly, School of Health Sciences, Faculty of Medicine, Larissa, Greece.
authors.forename: Anastasios E
authors.initials: AE
authors.lastname: Germenis
authors.affiliation: Department of Immunology and Histocompatibility, University of Thessaly, School of Health Sciences, Faculty of Medicine, Larissa, Greece. Electronic address: speletas@gmail.com.
authors.forename: Matthaios
authors.initials: M
authors.lastname: Speletas
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053265:B-Cell Activation Factor Receptor / Q000235:genetics*; D016638:Critical Illness; D003428:Cross Infection / Q000276:immunology / Q000382:microbiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018805:Sepsis / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D053265:B-Cell Activation Factor Receptor; C495345:TLR4 protein, human; C435926:TNFRSF13C protein, human; D051197:Toll-Like Receptor 4
keywords: BAFFR; C2 complement; Intensive care unit; Sepsis; TACI; TLR4