The Journal of Allergy and Clinical Immunology
Volume 124, Issue 6 , Pages 1358-1360.e1, December 2009

Placental transfer of allergen-specific IgG but not IgE from a specific immunotherapy–treated mother

  • Sabine Flicker, PhD

      Affiliations

    • Division of Immunopathology, Center for Physiology and Pathophysiology, Medical University of Vienna, Austria
    • ,
  • Katharina Marth, MD

      Affiliations

    • Division of Immunopathology, Center for Physiology and Pathophysiology, Medical University of Vienna, Austria
    • Christian Doppler Laboratory for Allergy Research Department of Pathophysiology, Center for Physiology and Pathophysiology, Medical University of Vienna, Austria
    • ,
  • Heinz Kofler, MD

      Affiliations

    • Allergieambulatorium, Hall, Austria
    • ,
  • Rudolf Valenta, MD

      Affiliations

    • Division of Immunopathology, Center for Physiology and Pathophysiology, Medical University of Vienna, Austria
    • Christian Doppler Laboratory for Allergy Research Department of Pathophysiology, Center for Physiology and Pathophysiology, Medical University of Vienna, Austria

Article Outline

 

To the Editor:

Several reports suggest that allergic sensitization can be influenced already in utero.1 Some studies indicate that allergic sensitization can occur in utero by transfer of allergens via the placenta to the child,2, 3 whereas others have argued against this possibility and suggest that allergen-specific IgE in cord blood does not reflect intrauterine sensitization but rather is the result of a transfer of maternal IgE to the fetus.4 However, whether IgE and in particular allergen-specific IgE can be transferred via the placenta to the child represents a controversial issue. The presence of allergen-specific IgE antibodies in children with specificities similar to those of their mothers has been reported in 2 studies,4, 5 whereas others suggested that the placenta represents a barrier for IgE antibodies.6, 7

We had the opportunity to study the antibody reactivity profiles in serum samples from a mother with birch and grass pollen allergy (IgE levels before specific immunotherapy: 18.50 kilo units [kU]/L total IgE, 1.8 kUA/L recombinant [r] Bet v 1, 2.48 kUA/L rPhl p 1 + rPhl p 5) who had received subcutaneous injection immunotherapy with birch and grass pollen extracts (Alutard SQ; ALK-Abelló, Hørsholm, Denmark) for 2 years before she became pregnant and delivered her baby as well as in the corresponding cord blood sample of her child using an array of purified allergen molecules. To the best of our knowledge, this is the first detailed analysis of allergen-specific IgE (Fig 1), IgG1, and IgG4 antibodies (Fig 2) to purified allergen molecules from several different allergen sources. The panel of 49 dot-blotted purified allergens included the most common inhalant, food,8 animal, latex, and insect allergens, and for control purposes, BSA (negative control), as shown in Fig 1, A (see this article's Table E1 in the Online Repository at www.jacionline.org). In addition, sera were tested for IgE reactivity to 89 microarrayed allergen molecules by using the Immuno solid-phase allergen chip (ISAC; Phadia, Uppsala, Sweden).9

  • View full-size image.
  • Fig 1. 

    A, Application pattern of dot-blotted recombinant (r) and natural (n) allergens and BSA. B, Detection of allergen-specific IgE antibodies to dot-blotted allergens in maternal serum and cord blood samples by autoradiography.

Using dot-blotted allergens as well as the allergen chip, we could demonstrate the distinct presence of IgE antibodies specific for the grass pollen allergens rPhl p 1, natural (n) Phl p 4, rPhl p 5, and rPhl p 13 and the major birch pollen allergen, rBet v 1, in the serum from the mother with allergy (Fig 1; data not shown), whereas no allergen-specific IgE antibodies to these allergens were found in cord blood (Fig 1).

By contrast, the IgG1 and IgG4 reactivity profiles detected in the mother's serum and in the cord blood sample were almost identical (Fig 2). IgG1 antibodies to rPhl p 1, nPhl p 4, rPhl p 5, rPhl p 6, nPhl p 13/rPhl p 13, rBet v 1, and rAln g 1, a birch pollen–related allergen from alder as well as to nDer p 1, rDer p 2, rDer p 10, rCla h 8, rAlt a 2, rHev b 1, rHev b 9, rHev b 10, rApi m 2, and rVes v 5 were found in the mother's serum and cord blood. Furthermore, both maternal serum and cord blood contained IgG4 antibodies to rPhl p 1, nPhl p 4, rPhl p 5, rPhl p 6, rPhl p 13, and rBet v 1 (Fig 2).

Our results thus indicate that IgG antibodies with defined allergen specificities are transferred from the mother to the child via the placenta, whereas allergen-specific IgE antibodies cannot cross the placenta barrier. IgG antibody reactivities, in particular IgG4 specific for grass and birch pollen allergens in the mother's serum, were more intense than those against allergens from other allergen sources and hence most likely have been induced by specific immunotherapy (Fig 2). However, IgG, in particular IgG1 specific for allergens other than those used for specific immunotherapy, was also found in the mother and cord blood.

We believe that this finding is important, because it has already been demonstrated in experimental animal models and in clinical studies that prenatal induction of allergen-specific IgG antibodies protects against allergen-induced sensitization and allergic inflammation in the offspring.10, 11, 12 The child studied by us has not developed any allergy (ie, to the age of 2 years). Several recent studies have shown that allergen-specific IgG antibodies induced by specific immunotherapy can protect against IgE-mediated allergic inflammation and against the allergen-induced boosting of IgE production.13, 14, 15, 16 It is therefore quite possible that active or passive allergen-specific vaccination of mothers may represent a feasible strategy for the prevention of allergic sensitization in childhood.

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Table E1. 

Tested allergens and the corresponding allergen sources
rPhl p 1Timothy grass pollen
rPhl p 2Timothy grass pollen
nPhl p 4Timothy grass pollen
rPhl p 5Timothy grass pollen
rPhl p 6Timothy grass pollen
rPhl p 7Timothy grass pollen
rPhl p 12Timothy grass pollen
nPhl p 13Timothy grass pollen
rPhl p 13Timothy grass pollen
rAmb a 1Ragweed pollen
rArt v 1Mugwort pollen
rBet v 1Birch pollen
rBet v 2Birch pollen
rMal d 1Apple
rAln g 1Alder pollen
rCor a 1Hazel pollen
rCan f 1Dog
rCan f 2Dog
rApi g 1Celery
rFel d 1Cat
rFeld 2Cat
nDer p 1House dust mite
rDer p 2House dust mite
rDer p 5House dust mite
rDer p 7House dust mite
rDer p 10House dust mite
rDer p 21House dust mite
rDer p 23House dust mite
rCla h 8Mold
rAlt a 1Mold
rAlt a 2Mold
rHev b 1Latex
rHev b 3Latex
rHev b 5Latex
rHev b 6Latex
rHev b 7Latex
rHev b 8Latex
rHev b 9Latex
rHev b 10Latex
rHev b 11Latex
rApi m 2Bee
rApi m 1Bee
rVes v 5Yellow jacket wasp
rCyp c 1Carp
Protein 10Wheat seeds8
Protein 37Wheat seeds8
Protein 112Wheat seeds8
Protein 126Wheat seeds8
rDau c 1Carrot
BSABovine serum albumin

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References 

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 Supported by grant 813003 of the Austrian Research Promotion Agency, grant F1815 of the Austrian Science Fund, and research grants from Biomay, Vienna, Austria; Phadia, Uppsala, Sweden; and the Christian Doppler Research Association, Vienna, Austria.

 Disclosure of potential conflict of interest: R. Valenta receives research support from the FWF Austrian Science Fund, Biomay, and Phadia. S. Flicker receives research support from the FFG Austrian Research Promotion Agency. The rest of the authors have declared that they have no conflict of interest.

PII: S0091-6749(09)01413-4

doi:10.1016/j.jaci.2009.09.024

The Journal of Allergy and Clinical Immunology
Volume 124, Issue 6 , Pages 1358-1360.e1, December 2009

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