House Dust Mite Exposure through Human Milk and Dust: What Matters for Child Allergy Risk?

Allergies are major noncommunicable diseases associated with significant morbidity, reduced quality of life, and high healthcare costs. Despite decades of research, it is still unknown if early-life exposure to indoor allergens plays a role in the development of IgE-mediated allergy and asthma. The objective of this study is to contribute to the identification of early-life risk factors for developing allergy. We addressed whether two different sources of house dust mite Der p 1 allergen exposure during early life, i.e., human milk and dust, have different relationships with IgE levels and asthma outcomes in children. We performed longitudinal analyses in 249 mother–child pairs using data from the PIAMA birth cohort. Asthma symptoms and serum total and specific IgE levels in children were available for the first 16 years of life. Der p 1 levels were measured in human milk and dust samples from infant mattresses. We observed that infant exposure to Der p 1 through human milk was associated with an increased risk of having high levels of serum IgE (top tertile > 150 kU/mL) in childhood as compared to infants exposed to human milk with undetectable Der p 1 [adjusted OR (95% CI) 1.83 (1.05–3.20) p = 0.0294]. The Der p 1 content in infant mattress dust was not associated with increased IgE levels in childhood. The risk of asthma and Der p 1 sensitization was neither associated with Der p 1 in human milk nor with Der p 1 in dust. In conclusion, high levels of IgE in childhood were associated with Der p 1 exposure through human milk but not exposure from mattress dust. This observation suggests that human milk is a source of Der p 1 exposure that is relevant to allergy development and fosters the need for research on the determinants of Der p 1 levels in human milk

PD01 - Respiratory allergens in human milk: potential impact on susceptibility to allergic airway disease

Poster discussion presentationInternational audienc

Quantitative and functional characterization of antibodies anti-Dermatophagoides pteronyssinus transference through placenta and maternal colostrum.

Existem fortes evidências de que a supressão da hipersensibilidade nos recém nascidos pode ser mediada pela transferência de anticorpos maternos, dependendo de sua concentração e especificidade, no entanto carece estudos sobre a eficácia em humanos. Realizamos este estudo a fim de caracterizar qualitativa e quantitativamente a transmissão de anticorpos direcionados ao principal alérgeno da poeira domiciliar (Der p) via placenta e colostro materno, assim como investigar o efeito da sensibilização materna ao Der p na transferência passiva destes anticorpos. Para tais objetivos, analisamos amostras de sangue materno, cordão umbilical e colostro de puérperas sensibilizadas. Demonstramos pela primeira vez que S-IgA anti-Der p pode ser transferida ao lactente em concentrações bastante variáveis e com alto índice de avidez, independente da sensibilização materna ao mesmo ácaro. Demonstramos também que o nível de IgG específica ao Der p é mais elevado em recém nascidos de mães sensibilizadas quando comparado aos de mães controle não sensibilizadas. Já a avidez específica da IgG anti-Der p foi muito semelhante entre as amostras pareadas de cordão umbilical e soro materno, assim como em amostras do grupo estudo e grupo controle.It is known that the incidence of allergic disease has been rising very fast in the last decade and nowadays affects thousands of children worldwide. For this reason, it is of great interest that efficient strategies of prevention of atopy should be applied in the first years of life or even before birth. The are strong evidences that the suppression of hypersensitivity in newborn can be mediated by the transference of maternal antibodies, depending on their concentration and specificity, however still little is known about the mechanisms involving, in special in humans. We made this study aiming to characterize qualitatively and quantitatively the antibodies transmission directed to the main home dust allergen (Dermatophagoides pteronyssinus; Der p) through placental transference and maternal breastfeeding as well as to investigate the maternal sensitizing effect against to Der p in passive transference of these antibodies. For those objectives, we quantified by ELISA, IgG anti-Der p in paired samples of maternal blood and umbilical cord and anti-Der p S-IgA in colostrums of sensitized mother (n=13) and not sensitized (n=26); and we analyzed the functional activity of the same antibodies by avidity assays. The sensibility was determined in maternal sera by specific RAST (Cap System® Pharmacia). We show by the first time that anti-Der p S-IgA is transferred to the infant in very variable concentrations and with high levels of avidity, but is not dependent of maternal sensitization. We believe that breastfeeding is important, because it supplies S-IgA with the capacity to neutralize in a specific manner and block the entrance of Der p through mucosa, in infant of RAST+ mothers as well as of RAST-. We also demonstrate that total and specific to Der p IgG levels are more elevated in newborns of sensitized mothers when compared to of those of control mothers and non-sensitized indicating that the maternal sensitizing can influence the fetal immune response. In the other hand, the specific avidity of anti-Der p IgG was very similar between paired samples of umbilical cord and maternal sera, as well as in samples of study group and control group, suggesting thar the avidity index of IgG does not influence on placental transfer of specific antibodies. Once that the maternal antibody transference represent a important mechanism for immunomodulation of allergic response, we expect that a better understanding of the influence of maternal sensitivity on passive transfer of specific antibodies to babies will contribute with advances in the elaboration of adequate strategies of prevention of allergic sensitivity with more efficient therapeutic results

Early Exposure to Respiratory Allergens by Placental Transfer and Breastfeeding.

The relationship between allergen exposure and the onset of or protection from allergic diseases remains unclear. Many factors could be related to immunological responses, such as the age when the exposure occurs, type of allergen, timing, dose, and allergen route. In this study, we investigated whether exposure to respiratory allergens could occur in pregnancy or early life. In particular, we assessed whether Der p 1 and Blo t 5, as well as specific antibodies against these allergens, could be detected in 90 paired cord blood and colostrum samples. Der p 1 was detected in 58.6% of colostrum and 29% of cord blood samples, whereas Blot 5 was positive in 41.3% and 9.6% of the samples, respectively. Similar to specific IgA, which could be detected in all samples for both mites, specific IgG was found in a high number of colostrum samples, 93.5% and 94.8% for Dp and Bt, respectively. Although allergens were not detected in all cord blood samples, a high percentage of them (≥95%) were positive for specific IgM to both mites in cord blood samples, suggesting that neonates can be exposed and sensitized to airborne allergens during pregnancy. Many studies have attempted to correlate allergen exposure or its prevention in early infancy with the onset of or protection from allergic diseases. However, conflicting and inconsistent data do not show a clear correlation with or suggest a way to prevent allergen sensitization. Nevertheless, these unconvincing results could be better understood if the relationship with many aspects of allergen exposure after pregnancy could be clarified. Thus, it is necessary to address basic issues related to allergen exposure, including the development of reproducible, standardized and reliable methods, and to determine how and where the exposure occurs

House Dust Mite Exposure through Human Milk and Dust: What Matters for Child Allergy Risk?

Allergies are major noncommunicable diseases associated with significant morbidity, reduced quality of life, and high healthcare costs. Despite decades of research, it is still unknown if early-life exposure to indoor allergens plays a role in the development of IgE-mediated allergy and asthma. The objective of this study is to contribute to the identification of early-life risk factors for developing allergy. We addressed whether two different sources of house dust mite Der p 1 allergen exposure during early life, i.e., human milk and dust, have different relationships with IgE levels and asthma outcomes in children. We performed longitudinal analyses in 249 mother-child pairs using data from the PIAMA birth cohort. Asthma symptoms and serum total and specific IgE levels in children were available for the first 16 years of life. Der p 1 levels were measured in human milk and dust samples from infant mattresses. We observed that infant exposure to Der p 1 through human milk was associated with an increased risk of having high levels of serum IgE (top tertile > 150 kU/mL) in childhood as compared to infants exposed to human milk with undetectable Der p 1 [adjusted OR (95% CI) 1.83 (1.05-3.20) p = 0.0294]. The Der p 1 content in infant mattress dust was not associated with increased IgE levels in childhood. The risk of asthma and Der p 1 sensitization was neither associated with Der p 1 in human milk nor with Der p 1 in dust. In conclusion, high levels of IgE in childhood were associated with Der p 1 exposure through human milk but not exposure from mattress dust. This observation suggests that human milk is a source of Der p 1 exposure that is relevant to allergy development and fosters the need for research on the determinants of Der p 1 levels in human milk

Correlations between Der p 1 and Blo t 5 in colostrum samples.

<p>Correlation coefficients were determined using Spearman’s tests.</p

Levels of Der p 1 and Blo t 5 allergens in the cord blood and colostrum samples.

<p>Horizontal lines represent the median detected allergen levels. All <i>p</i>-values were determined using the Wilcoxon signed rank test; ** <i>p</i> < 0.01; ***<i>p</i> < 0.001. </p

Correlation between specific IgA or IgG to Dp (A) or Bt (B) and Der p 1 (A) or Blo t 5 (B) allergens.

<p>Correlation coefficients were determined using Spearman’s tests; ** <i>p</i> < 0.01.</p