Maternal allergen-specific IgG might protect the child against allergic sensitization

Abstract

Background: Analysis 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.

Objective: We sought to analyze IgG reactivity to microarrayed allergens in mothers during pregnancy, in cord blood samples, in breast milk, and in infants in the first years of life with the aim to investigate whether maternal allergen-specific IgG can protect against IgE sensitization in the offspring.

Methods: Plasma samples from mothers during the third trimester, cord blood, breast milk collected 2 months after delivery, and plasma samples from children at 6, 12, and 60 months of age were analyzed for IgG reactivity to 164 microarrayed allergens (ImmunoCAP ISAC technology) in 99 families of the Swedish birth cohort Assessment of Lifestyle and Allergic Disease During Infancy (ALADDIN). IgE sensitizations to microarrayed allergens were determined at 5 years of age in the children.

Results: Allergen-specific IgG reactivity profiles in mothers, cord blood, and breast milk were highly correlated. Maternal allergen-specific IgG persisted in some children at 6 months. Children's allergen-specific IgG production occurred at 6 months and reflected allergen exposure. Children who were IgE sensitized against an allergen at 5 years of age had significantly higher allergen-specific IgG levels than nonsensitized children. For all 164 tested allergens, children from mothers with increased (>30 ISAC standardized units) specific plasma IgG levels against an allergen had no IgE sensitizations against that allergen at 5 years of age.

Conclusion: This is the first detailed analysis of the molecular IgG recognition profile in mothers and their children in early life. High allergen-specific IgG reactivity in the mother's plasma and breast milk and in cord blood seemed to protect against allergic sensitization at 5 years of age.

Keywords: Allergy; allergen; allergen-specific IgG; birth cohort; breast milk; cord blood; maternal IgG; microarrayed allergens; recombinant allergen; sensitization.

Fig 1

Percentages of IgE-sensitized children (n = 99) at 5 years of age, as detected by means of allergen extract-based Phadiatop and fx5 testing, classified as sensitized if the IgE level was 0.35 kU_A/L or greater and, as detected by testing with the panel of microarrayed allergen molecules, classified as sensitized at 0.3 ISU or greater.

Fig 2

Correlations between allergen-specific IgG levels (ISU-G) to each of the 164 microarrayed allergens in plasma samples of 99 mothers during the third trimester and corresponding plasma samples from their children at birth (cord blood) and 6 months, 12 months, and 5 years of age. Correlations of IgG levels in mothers with cord blood IgG (A), with IgG in children at 6 months (B), with IgG in children at 12 months (C), and with IgG in children at 5 years (D) are shown. Each dot is the IgG response to 1 allergen. Correlations are listed in Table III.

Fig 3

Correlations between IgE levels (y-axes, ISU) specific for 164 microarrayed allergens in 99 children at the age of 5 years with allergen-specific IgG in maternal plasma (A) and with allergen-specific IgG in cord blood samples (B; x-axes, ISU-G) are shown. Each data point represents a pair of maternal/cord blood IgG and corresponding children’s IgE levels at 5 years for 1 allergen. Each plot contains 99 families × 164 allergens = 16,236 data points. Vertical lines denote the observed cutoff of maternal allergen-specific IgG levels for the development of allergen-specific IgE sensitization. Horizontal lines indicate the threshold for IgE sensitization (≥0.3 ISU). All IgG and IgE levels of 0 ISU were substituted by a small value (IgE, 0.03; IgG, 0.005) to retain these data points in the figure on a logarithmic scale.

Fig 4

Allergen-specific IgG levels measured in 99 families (mothers’ plasma, cord blood, and children’s blood at 6 months, 12 months, and 5 years) for frequently recognized respiratory allergens (A, Phl p 1; B, Bet v 1; C, Fel d 1; D, Can f 1), a frequent venom allergen (E, Ves v 5), and food allergens (F, Ara h 1; G, Bos d 5; H, Gal d 1; and I, Tri a 36) are shown. x-axes, Samples; y-axes, IgG levels as ISU-G. Box plots display first quartiles, medians, and third quartiles, and whiskers represent the range of data within 1.5 times the interquartile range); outliers (>1.5 times interquartile range) and extreme values (>3 times interquartile range) are represented by open circles and asterisks, respectively.

Fig 4

Allergen-specific IgG levels measured in 99 families (mothers’ plasma, cord blood, and children’s blood at 6 months, 12 months, and 5 years) for frequently recognized respiratory allergens (A, Phl p 1; B, Bet v 1; C, Fel d 1; D, Can f 1), a frequent venom allergen (E, Ves v 5), and food allergens (F, Ara h 1; G, Bos d 5; H, Gal d 1; and I, Tri a 36) are shown. x-axes, Samples; y-axes, IgG levels as ISU-G. Box plots display first quartiles, medians, and third quartiles, and whiskers represent the range of data within 1.5 times the interquartile range); outliers (>1.5 times interquartile range) and extreme values (>3 times interquartile range) are represented by open circles and asterisks, respectively.

Fig 5

IgG levels specific for the most frequently recognized allergens (y-axes, ISU-G) in samples from children at 6 months, 12 months, and 5 years of age (x-axes) grouped according to the presence (≥0.3 ISU, green) or absence (blue) of allergen-specific IgE sensitization in children at 5 years of age. A, Phl p 1 (nonsensitized children, n = 80; sensitized children, n = 19). B, Bet v 1 (nonsensitized, n = 89; sensitized, n = 10). C, Ves v 5 (nonsensitized, n = 89; sensitized, n = 10). D, Fel d 1 (nonsensitized, n = 93; sensitized, n = 6). Box plots display first quartiles, medians, and third quartiles, and whiskers represent range of data within 1.5 times the interquartile range; outliers (>1.5 times interquartile range) and extreme values (>3 times interquartile range) are represented by open circles and asterisks, respectively. *P < .05, **P < . 01, and ***P < .001.