title: Sialylated Fetuin-A as a candidate predictive biomarker for successful grass pollen allergen immunotherapy.
abstract: BACKGROUND
  Eligibility to immunotherapy is based on the determination of IgE reactivity to a specific allergen by means of skin prick or in vitro testing. Biomarkers predicting the likelihood of clinical improvement during immunotherapy would significantly improve patient selection.
  
  
  METHODS
  Proteins were differentially assessed by using 2-dimensional differential gel electrophoresis and label-free mass spectrometry in pretreatment sera obtained from clinical responders and nonresponders within a cohort of 82 patients with grass pollen allergy receiving sublingual immunotherapy or placebo. Functional studies of Fetuin-A (FetA) were conducted by using gene silencing in a mouse asthma model, human dendritic cell in vitro stimulation assays, and surface plasmon resonance.
  
  
  RESULTS
  Analysis by using quantitative proteomics of pretreatment sera from patients with grass pollen allergy reveals that high levels of O-glycosylated sialylated FetA isoforms are found in patients exhibiting a strong decrease in rhinoconjunctivitis symptoms after sublingual immunotherapy. Although FetA is involved in numerous inflammatory conditions, its potential role in allergy is unknown. In vivo silencing of the FETUA gene in BALB/c mice results in a dramatic upregulation of airway hyperresponsiveness, lung resistance, and TH2 responses after allergic sensitization to ovalbumin. Both sialylated and nonsialytated FetA bind to LPS, but only the former synergizes with LPS and grass pollen or mite allergens to enhance the Toll-like receptor 4-mediated proallergic properties of human dendritic cells.
  
  
  CONCLUSIONS
  As a reflection of the patient's inflammatory status, pretreatment levels of sialylated FetA in the blood are indicative of the likelihood of clinical responses during grass pollen immunotherapy.
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: Noémie
authors.initials: N
authors.lastname: Caillot
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Bouley
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Jain
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Mariano
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Luce
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Horiot
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: Sabi
authors.initials: S
authors.lastname: Airouche
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Beuraud
authors.affiliation: INRA, UMR 1313 GABI, Research Center, Jouy-en-Josas, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Beauvallet
authors.affiliation: UPRES EA 220 and Clinical Research Department, Foch Hospital, Suresnes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Devillier
authors.affiliation: INSERM, UMR 996, Paris-Sud University, Châtenay-Malabry, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chollet-Martin
authors.affiliation: CNRS, UMR 6098, AFMB, Marseille, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Kellenberger
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Mascarell
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Chabre
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Batard
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Nony
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Lombardi
authors.affiliation: Research Department, Stallergenes Greer, Antony, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Baron-Bodo
authors.affiliation: Research Department, Stallergenes Greer, Antony, France. Electronic address: pmoingeon@stallergenes.com.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moingeon
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004311:Double-Blind Method; D020868:Gene Silencing; D006801:Humans; D008070:Lipopolysaccharides; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D006109:Poaceae / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000097:blood* / Q000628:therapy*; D063729:Sublingual Immunotherapy; D060749:alpha-2-HS-Glycoprotein / Q000032:analysis* / Q000235:genetics
chemical_list: D000485:Allergens; D015415:Biomarkers; D008070:Lipopolysaccharides; D060749:alpha-2-HS-Glycoprotein; D010047:Ovalbumin
keywords: Allergen immunotherapy; Fetuin-A; biomarker; serum