The Journal of Allergy and Clinical Immunology
Volume 119, Issue 5 , Pages 1164-1173, May 2007

Prenatal versus postnatal sensitization to environmental allergens in a high-risk birth cohort

  • Julie Rowe, PhD

      Affiliations

    • From the Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth
    • ,
  • Merci Kusel, MBBS, PhD

      Affiliations

    • From the Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth
    • ,
  • Barbara J. Holt, BSc

      Affiliations

    • From the Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth
    • ,
  • Devinda Suriyaarachchi, BSc(Hons)

      Affiliations

    • From the Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth
    • ,
  • Michael Serralha, BSc(Hons)

      Affiliations

    • From the Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth
    • ,
  • Elysia Hollams, PhD

      Affiliations

    • From the Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth
    • ,
  • Stephanie T. Yerkovich, PhD

      Affiliations

    • From the Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth
    • ,
  • Lily S. Subrata, PhD

      Affiliations

    • From the Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth
    • ,
  • Claire Ladyman, BSc

      Affiliations

    • From the Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth
    • ,
  • Agata Sadowska, BSc(Hons)

      Affiliations

    • From the Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth
    • ,
  • Jamie Gillett, BSc

      Affiliations

    • Princess Margaret Hospital for Children, Subiaco
    • ,
  • Elizabeth Fisher, BSc

      Affiliations

    • Princess Margaret Hospital for Children, Subiaco
    • ,
  • Richard Loh, FRACP

      Affiliations

    • Princess Margaret Hospital for Children, Subiaco
    • ,
  • Lars Soderstrom, MSc

      Affiliations

    • Phadia AB, Uppsala
    • Karolinska Institute, Stockholm
    • ,
  • Staffan Ahlstedt, PhD

      Affiliations

    • Phadia AB, Uppsala
    • Karolinska Institute, Stockholm
    • ,
  • Peter D. Sly, MD, FRACP, DSc

      Affiliations

    • From the Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth
    • ,
  • Patrick G. Holt, DSc

      Affiliations

    • From the Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth
    • Corresponding Author InformationReprint requests: Patrick G. Holt, DSc, Division of Cell Biology, Telethon Institute for Child Health Research, PO Box 855, West Perth WA 6872, Australia.

Received 14 November 2006; received in revised form 24 January 2007; accepted 15 February 2007. published online 06 April 2007.

Perth and Subiaco, Australia, and Uppsala and Stockholm, Sweden

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 IgG4 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 TH2 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-γ response capacity. HDM-induced T-cell responses in cord blood, although common, were unrelated to subsequent sensitization. Transient HDM-IgE (and IgG4) 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.

Conclusion

Priming of TH2 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 TH2 memory or IgE.

Clinical implications

These findings question the scientific basis for existing recommendations for allergen avoidance by high-risk women during pregnancy.

Key words: Atopy, cytokines, IgE, IgG4, T-cell memory, TH2

Abbreviations used: CBMC, Cord blood mononuclear cell, HDM, House dust mite, HR, High risk, OD, Odds ratio, RTE, Recent thymic emigrant, SPT, Skin prick test

 

 Supported by a grant from the National Health & Medical Research Council of Australia with supplementary support from the Food Allergy Initiative, New York.Disclosure of potential conflict of interest: L. Soderstrom and S. Ahlstedt are employed by Phadia AB, Uppsala, Sweden. The rest of the authors have declared that they have no conflict of interest.

PII: S0091-6749(07)00412-5

doi:10.1016/j.jaci.2007.02.016

The Journal of Allergy and Clinical Immunology
Volume 119, Issue 5 , Pages 1164-1173, May 2007

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