For most children, immunoglobulin E (IgE) sensitization to food and respiratory allergens begins during the first few years of life. However, maternal allergen-specific immunoglobulin G (IgG) is transferred to offspring during pregnancy, thereby possibly averting the evolution of allergic sensitization. Using IgE reactivity profiles from asymptomatic children in early life, it is possible to predict both the likelihood of a child developing symptoms later in life and the severity of those symptoms.

“Several factors are known or suspected to have an impact on allergic sensitization in children, both in terms of protection from, and facilitation of, IgE formation,” says Christian Lupinek, MD. “From allergen-specific immunotherapy (AIT), allergen specific IgG antibodies that block IgE binding to the respective allergen are known to be beneficial, as they can reduce symptom load in an allergen-specific manner when the patient is exposed to an allergen.”

 

Taking a Deeper Look

For a study published in the Journal of Allergy and Clinical Immunology, Dr. Lupinek and colleagues analyzed IgG reactivity to more than 160 microarrayed allergens in mothers during pregnancy, cord blood samples, breast milk, and infants in the first years of life (6 months, 12 months, and 5 years), exploring whether maternal allergen-specific IgG could protect offspring from IgE sensitization. The samples allowed studying both mother-to-child transferring of allergen-specific IgG and the subsequent production of allergen-specific antibodies in the infant.

“Children with IgE-sensitization also have higher IgG levels to the same respective allergen,” says Dr. Lupinek. “This demonstrates an obviously high general propensity in allergic subjects to mount an antibody response to harmless environmental antigens.”

 

Examining Key Findings

The study showed a high correlation among allergen-specific IgG reactivity profiles in mothers, cord blood, and breast milk. Maternal allergen-specific IgG remained for some children at 6 months. “The data clearly visualize the decline of the passively transferred maternal allergen-specific IgG, which are present at birth but hardly remain at 6 months of age,” says Dr. Lupinek.

Compared with nonsensitized children, those who were IgE sensitized against an allergen at age 5 showed monumentally elevated allergen-specific IgG levels at the same age. By contrast, mothers with elevated levels of IgG antibodies against an allergen in their blood exceeding 30 ISU-G had children without allergic IgE sensitizations toward that particular allergen—a finding consistent for all 164 tested allergens. In comparison, only children of mothers with lower allergen-specific IgG antibodies had IgE sensitization to allergens. “This implies that induction or passive transfer of allergen-specific IgG in pregnant women may facilitate prevention of allergic sensitization in their offspring,” says Dr. Lupinek.

When examining allergens against which children at age 5 were sensitized, the study team observed that to most allergens, no mother had mounted an IgG-response that exceeded a level of 30 ISU-G (Table). According to Dr. Lupinek, “This implies that both the spectrum and the level of allergen-specific IgG spontaneously formed in mothers would not be sufficient to convey protection from sensitization to their offspring.”

 

Assessing Implications

The study produces significant evidence that throughout pregnancy, elevated maternal allergen-specific IgG levels protect offspring from allergic sensitization, potentially providing new solutions in the prevention of allergic diseases. The initial post-natal months appear to be a key period for allergic sensitization, as levels of maternal IgG antibodies transferred to the child are already low at 6 months. “The observation that the passive transfer of allergen-specific IgG from mother to child may protect the child from getting sensitized to the respective allergens allows us to develop new strategies for the prevention of allergic sensitization” says Dr. Lupinek.

Allergen-specific immunotherapy (via vaccination) and passive immunization with IgG isolated from subjects with elevated levels of allergen-specific IgG can both increase the number of protective IgG antibodies in the plasma of pregnant women. AIT treatment of pregnant women can avert offspring’s development of IgE sensitization against correlating allergens. “In this context,” says Dr. Lupinek, “it seems to be relevant for the treatment to be effective that IgG-levels exceed a particular threshold (ie, 30 ISU-G).”

References

Lupinek C, Hochwallner H, Johansson C, et al. Maternal allergen-specific IgG might protect the child against allergic sensitization. J Allergy Clin Immunol. 2019;144(2):536-548. Available at https://www.jacionline.org/article/S0091-6749(19)30106-X/fulltext.