title: Prenatal versus postnatal sensitization to environmental allergens in a high-risk birth cohort.
abstract: BACKGROUND
  The timing of allergen sensitization is controversial, with conflicting evidence suggesting transplacental priming versus exclusively postnatal priming. Resolution of this question is important in relation to rational design of allergy prevention strategies, particularly the issue of allergen avoidance during pregnancy.
  
  
  OBJECTIVE
  To elucidate the kinetics of sensitization in high-risk children during their first 2 years of life.
  
  
  METHODS
  We prospectively studied house dust mite (HDM)-specific IgE and IgG(4) antibody production and associated T-cell immunity in a cohort of 200 high-risk infants. Parallel antibody studies tracked responses against a broader panel of inhalant and dietary allergens including peanut.
  
  
  RESULTS
  HDM-induced T(H)2 responses in PBMC from 6 months onward, particularly IL-4 and IL-5, correlated increasingly strongly with sensitization outcomes at 2 years, and a contrasting negative relationship was observed with IFN-gamma response capacity. HDM-induced T-cell responses in cord blood, although common, were unrelated to subsequent sensitization. Transient HDM-IgE (and IgG(4)) production frequently peaked at 6 or 12 months before returning to baseline, which suggests the onset of protective tolerance. This finding contrasted with progressively increasing HDM-IgE titers in children sensitized by 2 years of age. Comparably contrasting patterns were observed in peanut-specific responses in sensitized versus nonsensitized children.
  
  
  CONCLUSIONS
  Priming of T(H)2 responses associated with persistent HDM-IgE production occurs entirely postnatally, as HDM reactivity in cord blood seems nonspecific and is unrelated to subsequent development of allergen-specific T(H)2 memory or IgE.
  
  
  CONCLUSIONS
  These findings question the scientific basis for existing recommendations for allergen avoidance by high-risk women during pregnancy.
authors.affiliation: Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Australia.
authors.forename: Julie
authors.initials: J
authors.lastname: Rowe
authors.forename: Merci
authors.initials: M
authors.lastname: Kusel
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Holt
authors.forename: Devinda
authors.initials: D
authors.lastname: Suriyaarachchi
authors.forename: Michael
authors.initials: M
authors.lastname: Serralha
authors.forename: Elysia
authors.initials: E
authors.lastname: Hollams
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Yerkovich
authors.forename: Lily S
authors.initials: LS
authors.lastname: Subrata
authors.forename: Claire
authors.initials: C
authors.lastname: Ladyman
authors.forename: Agata
authors.initials: A
authors.lastname: Sadowska
authors.forename: Jamie
authors.initials: J
authors.lastname: Gillett
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fisher
authors.forename: Richard
authors.initials: R
authors.lastname: Loh
authors.forename: Lars
authors.initials: L
authors.lastname: Soderstrom
authors.forename: Staffan
authors.initials: S
authors.lastname: Ahlstedt
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Holt
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D002675:Child, Preschool; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007107:Immune System / Q000201:enzymology*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology*; D039981:Pyroglyphidae / Q000276:immunology; D012307:Risk Factors; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000485:Allergens; D007074:Immunoglobulin G; D015848:Interleukin-5; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma