title: Protein profiling of nasopharyngeal aspirates of hospitalized and outpatients revealed cytokines associated with severe influenza A(H1N1)pdm09 virus infections: A pilot study.
abstract: Influenza A viruses (IAV) mutate rapidly and cause seasonal epidemics and occasional pandemics, which result in substantial number of patient visits to the doctors and even hospitalizations. We aimed here to identify inflammatory proteins, which levels correlated to clinical severity of the disease. For this we analysed 102 cytokines and growth factors in human nasopharyngeal aspirate (NPA) samples of 27 hospitalized and 27 outpatients diagnosed with influenza A(H1N1)pdm09 virus infection. We found that the relative levels of monocyte differentiation antigen CD14, lipocalin-2 (LCN2), C-C-motif chemokine 20 (CCL20), CD147, urokinase plasminogen activator surface receptor (uPAR), pro-epidermal growth factor (EGF), trefoil factor 3 (TFF3), and macrophage migration inhibitory factor (MIF) were significantly lower (p<0.008), whereas levels of retinol-binding protein 4 (RBP4), C-X-C motif chemokine 5 (CXCL5), interleukin-8 (IL-8), complement factor D (CFD), adiponectin, and chitinase-3-like 1 (CHI3L1) were significantly higher (p<0.008) in NPA samples of hospitalized than non-hospitalized patients. While changes in CD14, LCN2, CCL20, uPAR, EGF, MIF, CXCL5, IL-8, adiponectin and CHI3L1 levels have already been correlated with severity of IAV infection in mice and humans, our study is the first to describe association of CD147, RBP4, TFF3, and CFD with hospitalization of IAV-infected patients. Thus, we identified local innate immune profiles, which were associated with the clinical severity of influenza infections.
authors.affiliation: The Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fu
authors.affiliation: The Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
authors.forename: Lana
authors.initials: L
authors.lastname: Gaelings
authors.affiliation: The Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Jalovaara
authors.affiliation: The Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland; Department of Virology, University of Turku, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Kakkola
authors.affiliation: The Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
authors.forename: Mervi T
authors.initials: MT
authors.lastname: Kinnunen
authors.affiliation: Department of Virology and Immunology, University of Helsinki and Helsinki University Hospital, HUSLAB, Finland.
authors.forename: Hannimari
authors.initials: H
authors.lastname: Kallio-Kokko
authors.affiliation: Department of Medicine, University of Helsinki, Finland.
authors.forename: Miia
authors.initials: M
authors.lastname: Valkonen
authors.affiliation: Department of Medicine, University of Helsinki, Finland; Inflammation Center, Helsinki University Hospital, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Kantele
authors.affiliation: The Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland. Electronic address: denis.kainov@helsinki.fi.
authors.forename: Denis E
authors.initials: DE
authors.lastname: Kainov
mesh_terms: D000328:Adult; D051926:Basigin / Q000032:analysis; D018925:Chemokines / Q000032:analysis*; D016207:Cytokines / Q000032:analysis*; D005260:Female; D006760:Hospitalization; D006801:Humans; D007113:Immunity, Innate; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009305:Nasopharynx / Q000276:immunology* / Q000821:virology; D010045:Outpatients; D010865:Pilot Projects; D040081:Protein Array Analysis; D054839:Retinol-Binding Proteins, Plasma / Q000032:analysis; D012720:Severity of Illness Index; D000071165:Trefoil Factor-3 / Q000032:analysis
chemical_list: C497886:BSG protein, human; D018925:Chemokines; D016207:Cytokines; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3; D051926:Basigin
keywords: Chemokine; Cytokine; Influenza virus; Nasopharyngeal aspirate