Maternal Immunization During Pregnancy Can Reduce IgE Response in Adult Offspring

Jacquelyn K. Beals, PhD

December 11, 2009

December 11, 2009 (Buenos Aires, Argentina) — A new study has demonstrated that inducing a Th1- or Th2-polarized immune response in pregnant mice can reduce offspring immunoglobulin (Ig)E response. An elicited maternal Th2 response was found to be more effective than a Th1 response for decreasing the subsequent IgE levels of adult offspring.

Martinus Løvik, MD, PhD, from the Department of Environmental Immunology, Norwegian Institute of Public Health in Oslo, and the Faculty of Medicine, Norwegian University of Science and Technology, in Trondheim, provided background for the study in his presentation here at the World Allergy Organization XXI World Allergy Congress.

Dr. Løvik noted that there is considerable 2-way communication between the immune systems of pregnant women and their developing offspring. Both prenatal and postnatal experience are known to be important in the subsequent development of allergy and asthma in children. Thus, it is logical that allergy and asthma prevention could be started during pregnancy.

The increasing occurrence of allergies in developed countries led to the hygiene hypothesis in 1989. The suggested mechanism, modified somewhat in 2005, proposed that proper regulatory T cell (Treg) development requires stimulation by bacteria, parasites, or other infectious agents. Treg cells produce cytokines that suppress inflammatory Th1 and Th2 cells and maintain their balance. Skewing toward Th1 cells increases susceptibility to autoimmune diseases such as diabetes; skewing toward Th2 cells increases allergy and asthma susceptibility.

In the current study, researchers induced a Th1- or Th2-polarized immune response in pregnant mice to investigate the sensitization of their offspring to the same allergen (ovalbumin). To sensitize the mice, on days 3 and 10 of pregnancy, they received ovalbumin along with aluminum hydroxide or pertussis toxin — both are Th2 adjuvants, substances that increase the antigenic response to ovalbumin. Another group of pregnant mice received ovalbumin plus bacterial DNA (CpG), a Th1 adjuvant.

"The mothers were given the allergen together with the adjuvants, so adjuvants were not given alone," explained Dr. Løvik. "Actually, that is a control that we would like to see here now but we do not have — the effects of the adjuvants given without allergen."

Six-week-old offspring were given ovalbumin in aluminum hydroxide followed by a booster dose after another 20 days. Five days later, investigators used enzyme-linked immunosorbent assay (ELISA) to determine serum levels of ovalbumin-specific IgE, IgG1, and IgG2a antibodies in mothers and their offspring.

"Mice are young adults by maybe 6 or 7 weeks," Dr. Løvik told Medscape Allergy and Immunology. "So we used them when they were 8 or 9 weeks [of age]. They are said to be immunologically mature at 9 to 10 weeks."

Levels of ovalbumin-specific IgE and IgG1 decreased strikingly in the offspring of mothers who received ovalbumin plus pertussis toxin. Levels of specific IgG2a antibodies increased. The pattern of specific IgE and IgG2a levels was similar but less striking in the offspring of mothers who received ovalbumin plus CpG. Combined exposure to the allergen ovalbumin and microbial adjuvants exerted a strong effect on the immune response of offspring, with specific IgE levels still decreased in adult offspring, depending on the adjuvant used.

Th2 responses elicited in mothers given pertussis toxin or aluminum hydroxide adjuvants reduced IgE levels in offspring more effectively than did the Th1 responses in mothers given CpG. In light of the understanding that Th1 activation decreases allergy susceptibility, the greater efficacy of maternal Th2 activation in lowering IgE levels in the offspring was surprising.

"These are very novel data, very exciting. It takes a bit of time to digest them, actually," session comoderator Stephen R. Durham, MD, FRCP, head of the Section for Allergy and Clinical Immunology at the National Heart and Lung Institute, Imperial College, and professor of Allergy and Respiratory Medicine at Royal Brompton Hospital, in London, United Kingdom, told Medscape Allergy and Immunology.

"The results were beautifully presented. There was a very clear effect in mice," Dr. Durham said, noting that the observations should be replicated and the study should be conducted with allergens other than ovalbumin in the mouse system. "That would be very important," he said. "I think that there are reservations about starting immunotherapy in [human] mothers. That's the real issue. At the moment, the current guidelines do not recommend immunization in mothers. That's not to say it's not a fascinating idea, but it would be very difficult to immediately transfer this information to humans," Dr. Durham observed.

"The other [point] . . . is whether we should be initiating immunotherapy before pregnancy. Maybe that's the approach that would be appropriate. With current guidelines, we're allowed to continue immunotherapy during pregnancy," said Dr. Durham. "So that would be the approach I would take."

Dr. Løvik also told Medscape Allergy and Immunology that "you can also immunize the [mouse] mothers before they get pregnant. No problem before they get pregnant, and you see the same effects in women. And of course you could, for example, use allergen vaccination, hypersensitization in women before they get pregnant."

This study was funded by the Norwegian Research Council and the Norwegian Institute of Public Health, both of which are noncommercial and fully independent. Dr. Løvik and Dr. Durham have disclosed no relevant financial relationships.

World Allergy Organization XXI World Allergy Congress (WAC): Abstract 865. Presented December 7, 2009.

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