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IgG transmitted from allergic mothers decreases allergic sensitization in breastfed offspring.

Matson AP, Thrall RS, Rafti E, Lingenheld EG, Puddington L - Clin Mol Allergy (2010)

Bottom Line: The mechanism(s) responsible for the reduced risk of allergic disease in breastfed infants are not fully understood.In offspring deficient in FcRn, we expected reduced levels of systemic allergen-specific IgG1, a consequence of decreased absorption of maternal IgG from the lumen of the neonatal gastrointestinal tract.FcRn expression was a major factor in determining how breastfed offspring of allergic mothers acquired levels of systemic allergen-specific IgG1 sufficient to inhibit allergic sensitization in this model.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut, USA. puddington@nso1.uchc.edu.

ABSTRACT

Background: The mechanism(s) responsible for the reduced risk of allergic disease in breastfed infants are not fully understood. Using an established murine model of asthma, we demonstrated previously that resistance to allergic airway disease transmitted from allergic mothers to breastfed offspring requires maternal B cell-derived factors.

Objective: The aim of this study was to investigate the role of offspring neonatal Fc receptor for IgG uptake by intestinal epithelial cells (FcRn) in this breast milk transferred protection from allergy.

Methods: Allergic airway disease was induced during pregnancy in C57BL/6 female mice. These allergic mothers foster nursed naive FcRn+/- or FcRn-/- progeny born to FcRn+/- females that were mated to C57BL/6J-FcRn-/- male mice. In offspring deficient in FcRn, we expected reduced levels of systemic allergen-specific IgG1, a consequence of decreased absorption of maternal IgG from the lumen of the neonatal gastrointestinal tract. Using this model, we were able to investigate how breast milk IgG affected offspring responses to allergic sensitization.

Results: Levels of maternal antibodies absorbed from the breast milk of allergic foster mothers were determined in weanling FcRn-sufficient or -deficient mice. Maternal transmission of allergen-specific IgG1 to breastfed FcRn-/- offspring was at levels 103-104 lower than observed in FcRn+/- or FcRn+/+ mice. Five weeks after weaning, when offspring were 8 wk old, mice were sensitized and challenged to evaluate their susceptibility to develop allergic airway disease. Protection, indicated by reduced parameters of disease (allergen-specific IgE in serum, eosinophilic inflammation in the airways and lung) were evident in FcRn-sufficient mice nursed as neonates by allergic mothers. In contrast, FcRn-deficient mice breastfed by the same mothers acquired limited, if any, protection from development of allergen-specific IgE and associated pathology.

Conclusions: FcRn expression was a major factor in determining how breastfed offspring of allergic mothers acquired levels of systemic allergen-specific IgG1 sufficient to inhibit allergic sensitization in this model.

No MeSH data available.


Related in: MedlinePlus

Absorption of OVA-specific IgG1 by breastfed offspring was determined by offspring FcRn expression. Naive C57BL/6J-FcRn+/- females (B6naive) were mated to C57BL/6J-FcRn-/- males. Progeny of this mating were FcRn+/- or FcRn-/-. C57BL/6J OVA-induced AAD (B6AAD) foster mothers were generated (as described in the Methods) and within 24 hours of delivery, pups with or without FcRn were adoptively nursed by B6AAD foster mothers. Serum was collected from FcRn+/+, FcRn+/-, or FcRn-/- offspring at weaning (24 days of life) and 52 days of life (1 week prior to OVA-immunization) and concentrations of OVA-specific Igs were measured by ELISA. OVA-specific Igs were absent from the serum of pups nursed by B6naive mothers (data not shown). Results are presented as 12-19 individual mice per group and the red line is the mean. There were no significant differences in serum concentrations of OVA-specific IgG1 antibodies between FcRn+/+ and FcRn+/- offspring at 24 days or 52 days of life. At 24 days of life, serum OVA-specific IgG1 concentrations were significantly lower in FcRn-/- offspring when compared to FcRn+/+ or FcRn+/- offspring (p ≤ 0.01). At 52 days of life, OVA-specific IgG1 antibodies were no longer detected in the serum of FcRn-/- offspring (limit of detection 30 ng/ml).
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Figure 3: Absorption of OVA-specific IgG1 by breastfed offspring was determined by offspring FcRn expression. Naive C57BL/6J-FcRn+/- females (B6naive) were mated to C57BL/6J-FcRn-/- males. Progeny of this mating were FcRn+/- or FcRn-/-. C57BL/6J OVA-induced AAD (B6AAD) foster mothers were generated (as described in the Methods) and within 24 hours of delivery, pups with or without FcRn were adoptively nursed by B6AAD foster mothers. Serum was collected from FcRn+/+, FcRn+/-, or FcRn-/- offspring at weaning (24 days of life) and 52 days of life (1 week prior to OVA-immunization) and concentrations of OVA-specific Igs were measured by ELISA. OVA-specific Igs were absent from the serum of pups nursed by B6naive mothers (data not shown). Results are presented as 12-19 individual mice per group and the red line is the mean. There were no significant differences in serum concentrations of OVA-specific IgG1 antibodies between FcRn+/+ and FcRn+/- offspring at 24 days or 52 days of life. At 24 days of life, serum OVA-specific IgG1 concentrations were significantly lower in FcRn-/- offspring when compared to FcRn+/+ or FcRn+/- offspring (p ≤ 0.01). At 52 days of life, OVA-specific IgG1 antibodies were no longer detected in the serum of FcRn-/- offspring (limit of detection 30 ng/ml).

Mentions: FcRn+/- or FcRn-/- offspring were nursed by B6AAD foster mothers using the adoptive nursing strategy (Figure 2), FcRn+/+ offspring were nursed by their own B6AAD birth mothers. Sera were obtained from FcRn+/+, FcRn+/-, or FcRn-/- offspring immediately prior and 4 weeks after weaning (at 24 and 52 days of life) for measurement of passively acquired maternal antibodies. As anticipated, at 24 days of life FcRn+/+ and FcRn+/- offspring had similar OVA-specific IgG1 serum concentrations (14,280 ± 1861 μg/ml and 6,954 ± 1259 μg/ml respectively; Figure 3). In contrast, FcRn-/- offspring displayed significantly reduced OVA-specific IgG1 serum concentrations (< 6 μg/ml). Thus, at weaning OVA-specific IgG1 antibodies were evident in the serum of FcRn-/- offspring nursed by B6AAD mothers, however the magnitude was 103-104 lower than that observed in FcRn+/+ and FcRn+/- offspring. No OVA-specific antibodies were detected in the serum of pups nursed by B6naive mothers (data not shown).


IgG transmitted from allergic mothers decreases allergic sensitization in breastfed offspring.

Matson AP, Thrall RS, Rafti E, Lingenheld EG, Puddington L - Clin Mol Allergy (2010)

Absorption of OVA-specific IgG1 by breastfed offspring was determined by offspring FcRn expression. Naive C57BL/6J-FcRn+/- females (B6naive) were mated to C57BL/6J-FcRn-/- males. Progeny of this mating were FcRn+/- or FcRn-/-. C57BL/6J OVA-induced AAD (B6AAD) foster mothers were generated (as described in the Methods) and within 24 hours of delivery, pups with or without FcRn were adoptively nursed by B6AAD foster mothers. Serum was collected from FcRn+/+, FcRn+/-, or FcRn-/- offspring at weaning (24 days of life) and 52 days of life (1 week prior to OVA-immunization) and concentrations of OVA-specific Igs were measured by ELISA. OVA-specific Igs were absent from the serum of pups nursed by B6naive mothers (data not shown). Results are presented as 12-19 individual mice per group and the red line is the mean. There were no significant differences in serum concentrations of OVA-specific IgG1 antibodies between FcRn+/+ and FcRn+/- offspring at 24 days or 52 days of life. At 24 days of life, serum OVA-specific IgG1 concentrations were significantly lower in FcRn-/- offspring when compared to FcRn+/+ or FcRn+/- offspring (p ≤ 0.01). At 52 days of life, OVA-specific IgG1 antibodies were no longer detected in the serum of FcRn-/- offspring (limit of detection 30 ng/ml).
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Figure 3: Absorption of OVA-specific IgG1 by breastfed offspring was determined by offspring FcRn expression. Naive C57BL/6J-FcRn+/- females (B6naive) were mated to C57BL/6J-FcRn-/- males. Progeny of this mating were FcRn+/- or FcRn-/-. C57BL/6J OVA-induced AAD (B6AAD) foster mothers were generated (as described in the Methods) and within 24 hours of delivery, pups with or without FcRn were adoptively nursed by B6AAD foster mothers. Serum was collected from FcRn+/+, FcRn+/-, or FcRn-/- offspring at weaning (24 days of life) and 52 days of life (1 week prior to OVA-immunization) and concentrations of OVA-specific Igs were measured by ELISA. OVA-specific Igs were absent from the serum of pups nursed by B6naive mothers (data not shown). Results are presented as 12-19 individual mice per group and the red line is the mean. There were no significant differences in serum concentrations of OVA-specific IgG1 antibodies between FcRn+/+ and FcRn+/- offspring at 24 days or 52 days of life. At 24 days of life, serum OVA-specific IgG1 concentrations were significantly lower in FcRn-/- offspring when compared to FcRn+/+ or FcRn+/- offspring (p ≤ 0.01). At 52 days of life, OVA-specific IgG1 antibodies were no longer detected in the serum of FcRn-/- offspring (limit of detection 30 ng/ml).
Mentions: FcRn+/- or FcRn-/- offspring were nursed by B6AAD foster mothers using the adoptive nursing strategy (Figure 2), FcRn+/+ offspring were nursed by their own B6AAD birth mothers. Sera were obtained from FcRn+/+, FcRn+/-, or FcRn-/- offspring immediately prior and 4 weeks after weaning (at 24 and 52 days of life) for measurement of passively acquired maternal antibodies. As anticipated, at 24 days of life FcRn+/+ and FcRn+/- offspring had similar OVA-specific IgG1 serum concentrations (14,280 ± 1861 μg/ml and 6,954 ± 1259 μg/ml respectively; Figure 3). In contrast, FcRn-/- offspring displayed significantly reduced OVA-specific IgG1 serum concentrations (< 6 μg/ml). Thus, at weaning OVA-specific IgG1 antibodies were evident in the serum of FcRn-/- offspring nursed by B6AAD mothers, however the magnitude was 103-104 lower than that observed in FcRn+/+ and FcRn+/- offspring. No OVA-specific antibodies were detected in the serum of pups nursed by B6naive mothers (data not shown).

Bottom Line: The mechanism(s) responsible for the reduced risk of allergic disease in breastfed infants are not fully understood.In offspring deficient in FcRn, we expected reduced levels of systemic allergen-specific IgG1, a consequence of decreased absorption of maternal IgG from the lumen of the neonatal gastrointestinal tract.FcRn expression was a major factor in determining how breastfed offspring of allergic mothers acquired levels of systemic allergen-specific IgG1 sufficient to inhibit allergic sensitization in this model.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut, USA. puddington@nso1.uchc.edu.

ABSTRACT

Background: The mechanism(s) responsible for the reduced risk of allergic disease in breastfed infants are not fully understood. Using an established murine model of asthma, we demonstrated previously that resistance to allergic airway disease transmitted from allergic mothers to breastfed offspring requires maternal B cell-derived factors.

Objective: The aim of this study was to investigate the role of offspring neonatal Fc receptor for IgG uptake by intestinal epithelial cells (FcRn) in this breast milk transferred protection from allergy.

Methods: Allergic airway disease was induced during pregnancy in C57BL/6 female mice. These allergic mothers foster nursed naive FcRn+/- or FcRn-/- progeny born to FcRn+/- females that were mated to C57BL/6J-FcRn-/- male mice. In offspring deficient in FcRn, we expected reduced levels of systemic allergen-specific IgG1, a consequence of decreased absorption of maternal IgG from the lumen of the neonatal gastrointestinal tract. Using this model, we were able to investigate how breast milk IgG affected offspring responses to allergic sensitization.

Results: Levels of maternal antibodies absorbed from the breast milk of allergic foster mothers were determined in weanling FcRn-sufficient or -deficient mice. Maternal transmission of allergen-specific IgG1 to breastfed FcRn-/- offspring was at levels 103-104 lower than observed in FcRn+/- or FcRn+/+ mice. Five weeks after weaning, when offspring were 8 wk old, mice were sensitized and challenged to evaluate their susceptibility to develop allergic airway disease. Protection, indicated by reduced parameters of disease (allergen-specific IgE in serum, eosinophilic inflammation in the airways and lung) were evident in FcRn-sufficient mice nursed as neonates by allergic mothers. In contrast, FcRn-deficient mice breastfed by the same mothers acquired limited, if any, protection from development of allergen-specific IgE and associated pathology.

Conclusions: FcRn expression was a major factor in determining how breastfed offspring of allergic mothers acquired levels of systemic allergen-specific IgG1 sufficient to inhibit allergic sensitization in this model.

No MeSH data available.


Related in: MedlinePlus