Does Maternal IgG Protect Infants from Allergen-Specific IgE Sensitization?

Passively acquired IgG antibodies are known to prevent immunization. The prototypic clinical application is the neonatal prevention of Rhesus D immunization by antirhesus antibodies. The prospect of a similar intervention in relation to IgE sensitization is the topic of an interesting article by Lupinek et al1Lupinek C. Hochwallner H. Johansson C. Mie A. Rigler E. Scheynius A. et al.Maternal allergen-specific IgG might protect the child against allergic sensitization.J Allergy Clin Immunol. 2019; 144: 536-548Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar: Does maternal IgG protect infants from allergen-specific IgE sensitization? The title of the article was carefully chosen: “Maternal allergen-specific IgG might protect the child against allergic sensitization,” but the title of the editorial by Schroeder2Schroeder Jr., H.W. A role for maternal IgG in protecting infants from allergen-specific IgE sensitization.J Allergy Clin Immunol. 2019; 144: 410-412Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar was more explicit: “A role for maternal IgG in protecting infants from allergen-specific IgE sensitization.” This statement is based on the conclusion that none of the children demonstrated IgE sensitization when the level of allergen-specific maternal IgG was higher than a given cutoff value.1Lupinek C. Hochwallner H. Johansson C. Mie A. Rigler E. Scheynius A. et al.Maternal allergen-specific IgG might protect the child against allergic sensitization.J Allergy Clin Immunol. 2019; 144: 536-548Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar However, the investigators used a very high cutoff value, and no statistical information on the predictive value of maternal allergen-specific IgG is presented. We would argue that the data on the large majority of the allergen tests are not informative, because the allergen is positive in fewer than 6 children.1Lupinek C. Hochwallner H. Johansson C. Mie A. Rigler E. Scheynius A. et al.Maternal allergen-specific IgG might protect the child against allergic sensitization.J Allergy Clin Immunol. 2019; 144: 536-548Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Only the results on the 3 most frequently sensitizing airborne allergens in their study, that is, Phl p 1 (n = 19), Bet v 1 (n = 10), and Fel d 1 (n = 6), are informative. However, the data on the relationship between the maternal antibody levels to these 3 allergens and the presence of sensitization in their child at age 5 years are not clear from the results shown. In an unpublished analysis of sera from 92 children from the prevention and incidence of asthma and mite allergy cohort,3Wijga A.H. Kerkhof M. Gehring U. de Jongste J.C. Postma D.S. Aalberse R.C. et al.Cohort profile: the prevention and incidence of asthma and mite allergy (PIAMA) birth cohort.Int J Epidemiol. 2014; 43: 527-535Crossref PubMed Scopus (106) Google Scholar we measured maternal allergen-specific IgG using radiolabeled affinity-purified major allergens from mite (Der p 1) and cat (Fel d 1) as described elsewhere.4Aalberse R.C. Lupinek C. Siroux V. Nadif R. Just J. Bousquet J. et al.sIgE and sIgG to airborne atopic allergens: coupled rather than inversely related responses.Allergy. 2018; 73: 2239-2242Crossref PubMed Scopus (6) Google Scholar Sixty of these children were negative (<0.35 kUA IgE/L) for Dermatophagoides pteronyssinus. The mothers of 8 (13%) of these mite-negative children had higher IgG anti–Der p 1 antibody levels compared with any of the 32 mite-positive children (see Fig 1, A). However, this negative association between the level of maternal allergen-specific IgG and mite sensitization in the child was not statistically significant by Mann-Whitney test (P > .1), but marginally significant by chi-square analysis (P = .077). In contrast, maternal IgG levels to Fel d 1 were higher in 3 of 13 cat-sensitized children (23%) than in any of the 79 mothers of children without IgE to cat. This positive association was statistically not significant by Mann-Whitney test (P > .1), but significant by chi-square analysis (P < .001). We conclude that a protective effect of allergen-specific maternal IgG remains a very interesting hypothesis, but as yet needs more extensive studies for validation. Effects on persistent sensitizations, particularly to allergens from pollen and mites, are most likely to be amenable to interventions, because these IgG levels are low in most mothers. The logical next step would be to have a closer look at existing data from cohort studies with mother-child pairs in which the mother received immunotherapy with airborne allergens during pregnancy and the level of allergen-specific IgE was monitored in childhood. Because the effect of maternal IgG is likely to be dependent on allergen exposure during early infancy, it might be relevant to take the child's date of birth into account. The data shown were obtained thanks to the participants of the prevention and incidence of asthma and mite allergy project coordinated by Bert Brunekreef. The serological assays were performed by Janny de Vrieze and Ellen Vermeulen. Maternal allergen-specific IgG might protect the child against allergic sensitizationJournal of Allergy and Clinical ImmunologyVol. 144Issue 2PreviewAnalysis of allergen-specific IgE responses in birth cohorts with microarrayed allergens has provided detailed information regarding the evolution of specific IgE responses in children. High-resolution data regarding early development of allergen-specific IgG are needed. Full-Text PDF Open AccessReplyJournal of Allergy and Clinical ImmunologyVol. 144Issue 5PreviewWe have recently reported that mothers with elevated allergen-specific IgG levels close to birth could transmit allergen-specific IgG antibodies to their children and, when the allergen-specific IgG levels were above a certain threshold as shown in maternal blood samples close to birth and in cord blood samples, the children did not develop allergen-specific IgE sensitizations against these allergens up to the age of 5 years.1 In a Correspondence, Aalberse et al2 consider our assumption “that maternal allergen-specific IgG might protect the child against allergic sensitization” interesting but suggest that it needs more extensive studies for validation. Full-Text PDF