title: Functional analysis via standardized whole-blood stimulation systems defines the boundaries of a healthy immune response to complex stimuli.
abstract: Standardization of immunophenotyping procedures has become a high priority. We have developed a suite of whole-blood, syringe-based assay systems that can be used to reproducibly assess induced innate or adaptive immune responses. By eliminating preanalytical errors associated with immune monitoring, we have defined the protein signatures induced by (1) medically relevant bacteria, fungi, and viruses; (2) agonists specific for defined host sensors; (3) clinically employed cytokines; and (4) activators of T cell immunity. Our results provide an initial assessment of healthy donor reference values for induced cytokines and chemokines and we report the failure to release interleukin-1α as a common immunological phenotype. The observed naturally occurring variation of the immune response may help to explain differential susceptibility to disease or response to therapeutic intervention. The implementation of a general solution for assessment of functional immune responses will help support harmonization of clinical studies and data sharing.
authors.affiliation: Center for Human Immunology, Institut Pasteur, 75015 Paris, France; INSERM U818, 75015 Paris, France; Laboratory of Dendritic Cell Immunobiology, Department of Immunology, Institut Pasteur, 75015 Paris, France.
authors.forename: Darragh
authors.initials: D
authors.lastname: Duffy
authors.affiliation: Center for Human Immunology, Institut Pasteur, 75015 Paris, France; Center for Bioinformatics, Institut Pasteur, 75015 Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Rouilly
authors.affiliation: Center for Human Immunology, Institut Pasteur, 75015 Paris, France.
authors.forename: Valentina
authors.initials: V
authors.lastname: Libri
authors.affiliation: Center for Human Immunology, Institut Pasteur, 75015 Paris, France.
authors.forename: Milena
authors.initials: M
authors.lastname: Hasan
authors.affiliation: Center for Human Immunology, Institut Pasteur, 75015 Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Beitz
authors.affiliation: Center for Human Immunology, Institut Pasteur, 75015 Paris, France.
authors.forename: Mikael
authors.initials: M
authors.lastname: David
authors.affiliation: Center for Human Immunology, Institut Pasteur, 75015 Paris, France; INSERM U818, 75015 Paris, France; Laboratory of Dendritic Cell Immunobiology, Department of Immunology, Institut Pasteur, 75015 Paris, France.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Urrutia
authors.affiliation: INSERM U818, 75015 Paris, France; Laboratory of Dendritic Cell Immunobiology, Department of Immunology, Institut Pasteur, 75015 Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Bisiaux
authors.affiliation: Myriad Rules Based Medicine, Inc., Austin, TX 78759, USA.
authors.forename: Samuel T
authors.initials: ST
authors.lastname: Labrie
authors.affiliation: Center for the Integration of Clinical Research, Institut Pasteur, 75015 Paris, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Dubois
authors.affiliation: Laboratory of Biology & Genetics of the Bacterial Cell Wall, Department of Microbiology, Institut Pasteur, 75015 Paris, France; INSERM, Equipe Avenir, 75015 Paris, France.
authors.forename: Ivo G
authors.initials: IG
authors.lastname: Boneca
authors.affiliation: Center for the Integration of Clinical Research, Institut Pasteur, 75015 Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Delval
authors.affiliation: Center for Human Immunology, Institut Pasteur, 75015 Paris, France; INSERM U818, 75015 Paris, France; Laboratory of Dendritic Cell Immunobiology, Department of Immunology, Institut Pasteur, 75015 Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Center for Human Immunology, Institut Pasteur, 75015 Paris, France; Laboratory of Immunoregulation, Department of Immunology, Institut Pasteur, 75015 Paris, France.
authors.forename: Lars
authors.initials: L
authors.lastname: Rogge
authors.affiliation: Myriad Rules Based Medicine, Inc., 72770 Reutlingen, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Schmolz
authors.affiliation: Laboratory of Human Evolutionary Genetics, Department of Genomes & Genetics, Institut Pasteur, 75015 Paris, France; CNRS URA3012, 75015 Paris, France. Electronic address: quintana@pasteur.fr.
authors.forename: Lluis
authors.initials: L
authors.lastname: Quintana-Murci
authors.affiliation: Center for Human Immunology, Institut Pasteur, 75015 Paris, France; INSERM U818, 75015 Paris, France; Laboratory of Dendritic Cell Immunobiology, Department of Immunology, Institut Pasteur, 75015 Paris, France; INSERM UMS20, 75015 Paris, France. Electronic address: albertm@pasteur.fr.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Albert
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D015166:Monitoring, Immunologic / Q000379:methods* / Q000592:standards; D012016:Reference Values; D015203:Reproducibility of Results
chemical_list: D000941:Antigens; D016207:Cytokines; D018836:Inflammation Mediators