Identification of the major immune differences in severe asthmatic children according to their atopic dermatitis status.

Severe asthma (SA) affects 2% to 5% of asthmatic children. Atopic dermatitis can affect up to 34% of children with SA (cwSA). Atopic dermatitis and asthma share common genetic and immunological features. However, not all children with SA suffer from AD, and it remains unclear whether the overall immune profiles of these children are similar. In this study, seventeen cwSA (9.8 [7.1-13.2] years; seven with and ten without AD) were enrolled. Bronchoalveolar lavage (BAL) and blood samples were collected from these patients. Seventy-three cytokines/chemokines and distinct immune T cell populations were evaluated in blood and BAL. We found that BAL and blood immune profiles of cwSA with and without AD were globally similar. However, specific differences were observed, namely lower frequency of Tc2, Th17 and IL-17-producing mucosal associated invariant T (MAIT-17) cells and higher CD8/CD4 ratio and IL-22 concentrations in BAL and of CCL19 concentrations in plasma from cwSA with AD. Further, in contrast with cwSA without AD, we found a positive correlation between a set of plasma cytokines and almost all cytokines in BAL in cwSA with AD. In conclusion, this study shows the major immune differences between cwSA with and without AD in BAL and blood suggesting that distinct endotypes may be implicated in the inflammatory responses observed in these pediatric patients.

Long-term exposure from perinatal life to food-grade TiO2 alters intestinal homeostasis and predisposes to food allergy in young mice.

BACKGROUND: Food allergy (FA) is an inappropriate immunological response to food proteins resulting from an impaired induction of oral tolerance. Various early environmental factors can affect the establishment of intestinal homeostasis, predisposing to FA in early life. In this context, we aimed to assess the effect of chronic perinatal exposure to food-grade titanium dioxide (fg-TiO2 ), a common food additive. METHODS: Dams were fed a control versus fg-TiO2 -enriched diet from preconception to weaning, and their progeny received the same diet at weaning. A comprehensive analysis of baseline intestinal and systemic homeostasis was performed in offspring 1 week after weaning by assessing gut barrier maturation and microbiota composition, and local and systemic immune system and metabolome. The effect of fg-TiO2 on the susceptibility of progeny to develop oral tolerance versus FA to cow's milk proteins (CMP) was performed starting at the same baseline time-point, using established models. Sensitization to CMP was investigated by measuring ß-lactoglobulin and casein-specific IgG1 and IgE antibodies, and elicitation of the allergic reaction by measuring mouse mast cell protease (mMCP1) in plasma collected after an oral food challenge. RESULTS: Perinatal exposure to fg-TiO2 at realistic human doses led to an increased propensity to develop FA and an impaired induction of oral tolerance only in young males, which could be related to global baseline alterations in intestinal barrier, gut microbiota composition, local and systemic immunity, and metabolism. CONCLUSIONS: Long-term perinatal exposure to fg-TiO2 alters intestinal homeostasis establishment and predisposes to food allergy, with a clear gender effect.

Prenatal dietary exposure to mixtures of chemicals is associated with allergy or respiratory diseases in children in the ELFE nationwide cohort.

INTRODUCTION: Prenatal exposure to environmental chemicals may be associated with allergies later in life. We aimed to examine the association between prenatal dietary exposure to mixtures of chemicals and allergic or respiratory diseases up to age 5.5 y. METHODS: We included 11,638 mother-child pairs from the French "Étude Longitudinale Française depuis l'Enfance" (ELFE) cohort. Maternal dietary exposure during pregnancy to eight mixtures of chemicals was previously assessed. Allergic and respiratory diseases (eczema, food allergy, wheezing and asthma) were reported by parents between birth and age 5.5 years. Associations were evaluated with adjusted logistic regressions. Results are expressed as odds ratio (OR[95%CI]) for a variation of one SD increase in mixture pattern. RESULTS: Maternal dietary exposure to a mixture composed mainly of trace elements, furans and polycyclic aromatic hydrocarbons (PAHs) was positively associated with the risk of eczema (1.10 [1.05; 1.15]), this association was consistent across sensitivity analyses. Dietary exposure to one mixture of pesticides was positively associated with the risk of food allergy (1.10 [1.02; 1.18]), whereas the exposure to another mixture of pesticides was positively but slightly related to the risk of wheezing (1.05 [1.01; 1.08]). This last association was not found in all sensitivity analyses. Dietary exposure to a mixture composed by perfluoroalkyl acids, PAHs and trace elements was negatively associated with the risk of asthma (0.89 [0.80; 0.99]), this association was consistent across sensitivity analyses, except the complete-case analysis. CONCLUSION: Whereas few individual chemicals were related to the risk of allergic and respiratory diseases, some consistent associations were found between prenatal dietary exposure to some mixtures of chemicals and the risk of allergic or respiratory diseases. The positive association between trace elements, furans and PAHs and the risk of eczema, and that between pesticides mixtures and food allergy need to be confirmed in other studies. Conversely, the negative association between perfluoroalkyl acids, PAHs and trace elements and the risk of asthma need to be further explored.

Characteristics of infant formula consumed in the first months of life and allergy in the EDEN mother-child cohort.

The evidence regarding the association between infant formula (IF) composition and the prevention of allergy and respiratory diseases remains sparse and inconclusive. This study aimed to evaluate whether some IF characteristics were associated with the risk of allergy or respiratory diseases in childhood. Among 1243 formula-fed children from the EDEN mother-child cohort, IF characteristics concerning long-chain polyunsaturated fatty acids (LCPUFAs) enrichment, prebiotic/probiotic enrichment, and hydrolysis of proteins were identified from the ingredients list. Eczema, wheezing, food allergy, asthma, and allergic rhinitis up to age 8 years were prospectively collected and summarized into four allergic and respiratory multimorbidity clusters. Associations between 4-month IF characteristics and risk of allergy or respiratory diseases were tested using logistic regressions adjusted on main confounders. The consumption of LCPUFA-enriched formula was not linked to allergic and respiratory multimorbidity clusters, but to a lower risk of any allergy, eczema, and wheezing. Probiotic-enriched formula consumption was associated with a lower risk of belonging to the 'Allergy without asthma' cluster (odds ratio [OR] [95% confidence interval, CI] = 0.63 [0.40-0.99]), and consumption of a formula enriched in Bifidobacterium lactis was associated with a lower risk of any allergy (OR [95% CI] = 0.59 [0.41-0.85]). Partially hydrolysed formula (pHF) consumption was associated with a higher risk of belonging to the 'Allergy without asthma' cluster (OR [95% CI] = 2.73 [1.65-4.51]). This study confirms the positive association between pHF consumption and the risk of allergy found in previous observational studies and suggests that consumption of LCPUFA-enriched or probiotic-enriched formula was associated with a lower risk of allergy.

Immunodominant conformational and linear IgE epitopes lie in a single segment of Ara h 2.

BACKGROUND: Contribution of conformational epitopes to the IgE reactivity of peanut allergens Ara h 2 and Ara h 6 is at least as important as that of the linear epitopes. However, little is known about these conformational IgE-binding epitopes. OBJECTIVE: We investigated the distribution of conformational epitopes on chimeric 2S-albumins. METHODS: Recombinant chimeras were generated by exchanging structural segments between Ara h 2 and Ara h 6. Well-refolded chimeras, as verified by circular dichroism analysis, were then used to determine the epitope specificity of mAbs by performing competitive inhibition of IgG binding. Furthermore, we delineated the contribution of each segment to the overall IgE reactivity of both 2S-albumins by measuring the chimeras' IgE-binding capacity with sera from 21 patients allergic to peanut. We finally assessed chimeras' capacity to trigger mast cell degranulation. RESULTS: Configuration of the conformational epitopes was preserved in the chimeras. Mouse IgG mAbs, raised against natural Ara h 6, and polyclonal human IgE antibodies recognized different conformational epitopes distributed all along Ara h 6. In contrast, we identified human IgG mAbs specific to different Ara h 2 linear or conformational epitopes located in all segments except the C-terminal one. The major conformational IgE-binding epitope of Ara h 2 was located in a segment located between residues 33 and 81 that also contains the major linear hydroxyproline-containing epitope. Accordingly, this segment is critical for the capacity of Ara h 2 to induce mast cell degranulation. CONCLUSIONS: Chimeric 2S-albumins provide new insights on the conformational IgE-binding epitopes of Ara h 2 and Ara h 6. Proximity of the immunodominant linear and conformational IgE-binding epitopes probably contributes to the high allergenic potency of Ara h 2.

Enrichment of infant formula with long-chain polyunsaturated fatty acids and risk of infection and allergy in the nationwide ELFE birth cohort.

BACKGROUND: The new European regulations require the enrichment of formulas with docosahexaenoic acid (DHA) because of the positive effects of long-chain polyunsaturated fatty acids (LCPUFAs) on neurodevelopment and visual acuity. In this observational study, we aimed to evaluate whether the consumption of LCPUFA-enriched formula was associated with the risk of infection and allergy in early childhood. METHODS: Analyses involved data from 8389 formula-fed infants from the ELFE birth cohort. Formula enrichment was identified from the list of ingredients of the formula consumed at 2 months. Infections (gastrointestinal, lower respiratory tract [LRTI], upper respiratory tract) and allergies (wheezing, itchy rash, asthma medication, food allergy) from age 2 months to 5.5 years were reported by parents during follow-up surveys. Multivariable logistic regression models were used to assess associations between the consumption of LCPUFA-enriched formula and the risk of infection and allergy. RESULTS: Among formula-fed infants at 2 months, 36% consumed formula enriched with DHA and arachidonic acid (ARA), and 11% consumed formula additionally enriched with eicosapentaenoic acid (EPA). Enriched formula consumption was not associated with infection or allergy, except for an association between consumption of DHA/ARA/EPA-enriched formula and lower use of asthma medications. Furthermore, as compared with non-DHA/ARA/EPA-enriched formula, consumption of formula with high EPA content (≥3.2 mg/100 kcal) was related to lower risk of LRTI and lower use of asthma medications. CONCLUSION: This study suggests that consumption of DHA/ARA/EPA-enriched formula (especially those with high EPA content) is associated with a lower risk of LRTI and lower use of asthma medications.

Role of dietary fiber in promoting immune health-An EAACI position paper.

Microbial metabolism of specific dietary components, such as fiber, contributes to the sophisticated inter-kingdom dialogue in the gut that maintains a stable environment with important beneficial physiological, metabolic, and immunological effects on the host. Historical changes in fiber intake may be contributing to the increase of allergic and hypersensitivity disorders as fiber-derived metabolites are evolutionarily hardwired into the molecular circuitry governing immune cell decision-making processes. In this review, we highlight the importance of fiber as a dietary ingredient, its effects on the microbiome, its effects on immune regulation, the importance of appropriate timing of intervention to target any potential window of opportunity, and potential mechanisms for dietary fibers in the prevention and management of allergic diseases. In addition, we review the human studies examining fiber or prebiotic interventions on asthma and respiratory outcomes, allergic rhinitis, atopic dermatitis, and overall risk of atopic disorders. While exposures, interventions, and outcomes were too heterogeneous for meta-analysis, there is significant potential for using fiber in targeted manipulations of the gut microbiome and its metabolic functions in promoting immune health.

Enrichment of Formula in Probiotics or Prebiotics and Risk of Infection and Allergic Diseases up to Age 5.5 Years in the Nationwide Etude Longitudinale Française depuis l'Enfance (ELFE) Cohort.

BACKGROUND: An increasing number of infant and follow-on formulas are enriched with probiotics and/or prebiotics; however, evidence for health effects of such enrichment in early childhood remains inconclusive. OBJECTIVES: The present study aimed to assess whether the consumption of formula enriched with probiotics or prebiotics was associated with the risk of infection and allergic diseases in early childhood. METHODS: Analyses involved data for 8389 formula-fed children from the Etude Longitudinale Française depuis l'Enfance (ELFE) cohort. Enrichment of the formula with probiotics or prebiotics that was consumed from the age of 2-10 mo was identified by the formula ingredient list. Lower respiratory tract infection (LRTI), upper respiratory tract infection (URTI), gastrointestinal infection, wheezing, asthma, food allergy, and itchy rash were prospectively reported by parents up to the age of 5.5 y. Adjusted logistic regression models were used to assess associations between the consumption of enriched formula and risk of infection and allergic diseases. RESULTS: Aged 2 mo, more than half of formula-fed infants consumed the probiotic-enriched formula and only 1 in 10 consumed the prebiotic-enriched formula. Consumption of the Bifidobacterium lactis-enriched formula at 2 mo was associated with a lower risk of LRTI [OR (95% CI) = 0.84 (0.73-0.96)]. Consumption of the Bifidobacterium breve-enriched formula up to 6 mo was associated with a higher risk of LRTI [OR (95% CI) = 1.75 (1.29-2.38)] and asthma [OR (95% CI) = 1.95 (1.28-2.97)], whereas its consumption from 6 to 10 mo was associated with a lower risk of LRTI [OR (95% CI) = 0.64 (0.48-0.86)] and asthma [OR (95% CI) = 0.59 (0.40-0.88)]. Moreover, the consumption of Streptococcus thermophilus from 6 to 10 mo was associated with a higher risk of asthma [OR (95% CI) = 1.84 (1.29-2.63)]. No significant association was found for gastrointestinal infection, food allergy, and itchy rash. Overall, the consumption of prebiotic-enriched formula was not significantly associated with infection and allergy risk. CONCLUSIONS: Associations between the consumption of probiotic-enriched formula and risk of respiratory symptoms differ according to the strain considered and consumption period. Further well-designed studies are needed to confirm these results.

Enrichment of Formula in Probiotics or Prebiotics and Risk of Infection and Allergic Diseases up to Age 5.5 Years in the Nationwide Etude Longitudinale Française depuis l'Enfance (ELFE) Cohort.

BACKGROUND: An increasing number of infant and follow-on formulas are enriched with probiotics and/or prebiotics; however, evidence for health effects of such enrichment in early childhood remains inconclusive. OBJECTIVES: The present study aimed to assess whether the consumption of formula enriched with probiotics or prebiotics was associated with the risk of infection and allergic diseases in early childhood. METHODS: Analyses involved data for 8389 formula-fed children from the Etude Longitudinale Française depuis l'Enfance (ELFE) cohort. Enrichment of the formula with probiotics or prebiotics that was consumed from the age of 2-10 mo was identified by the formula ingredient list. Lower respiratory tract infection (LRTI), upper respiratory tract infection (URTI), gastrointestinal infection, wheezing, asthma, food allergy, and itchy rash were prospectively reported by parents up to the age of 5.5 y. Adjusted logistic regression models were used to assess associations between the consumption of enriched formula and risk of infection and allergic diseases. RESULTS: Aged 2 mo, more than half of formula-fed infants consumed the probiotic-enriched formula and only 1 in 10 consumed the prebiotic-enriched formula. Consumption of the Bifidobacterium lactis-enriched formula at 2 mo was associated with a lower risk of LRTI [OR (95% CI) = 0.84 (0.73-0.96)]. Consumption of the Bifidobacterium breve-enriched formula up to 6 mo was associated with a higher risk of LRTI [OR (95% CI) = 1.75 (1.29-2.38)] and asthma [OR (95% CI) = 1.95 (1.28-2.97)], whereas its consumption from 6 to 10 mo was associated with a lower risk of LRTI [OR (95% CI) = 0.64 (0.48-0.86)] and asthma [OR (95% CI) = 0.59 (0.40-0.88)]. Moreover, the consumption of Streptococcus thermophilus from 6 to 10 mo was associated with a higher risk of asthma [OR (95% CI) = 1.84 (1.29-2.63)]. No significant association was found for gastrointestinal infection, food allergy, and itchy rash. Overall, the consumption of prebiotic-enriched formula was not significantly associated with infection and allergy risk. CONCLUSIONS: Associations between the consumption of probiotic-enriched formula and risk of respiratory symptoms differ according to the strain considered and consumption period. Further well-designed studies are needed to confirm these results.

Development of incurred chocolate bars and broth powder with six fully characterised food allergens as test materials for food allergen analysis.

The design and production of incurred test materials are critical for the development and validation of methods for food allergen analysis. This is because production and processing conditions, together with the food matrix, can modify allergens affecting their structure, extractability and detectability. For the ThRAll project, which aims to develop a mass spectrometry-based reference method for the simultaneous accurate quantification of six allergenic ingredients in two hard to analyse matrices. Two highly processed matrices, chocolate bars and broth powder, were selected to incur with six allergenic ingredients (egg, milk, peanut, soy, hazelnut and almond) at 2, 4, 10 and 40 mg total allergenic protein/kg food matrix using a pilot-scale food manufacturing plant. The allergenic activity of the ingredients incurred was verified using food-allergic patient serum/plasma IgE, the homogeneity of the incurred matrices verified and their stability at 4 °C assessed over at least 30-month storage using appropriate enzyme-linked immunosorbent assays (ELISA). Allergens were found at all levels from the chocolate bar and were homogenously distributed, apart from peanut and soy which could only be determined above 4 mg total allergenic ingredient protein/kg. The homogeneity assessment was restricted to analysis of soy, milk and peanut for the broth powder but nevertheless demonstrated that the allergens were homogeneously distributed. All the allergens tested were found to be stable in the incurred matrices for at least 30 months demonstrating they are suitable for method development.

Circulating Ara h 6 as a marker of peanut protein absorption in tolerant and allergic humans following ingestion of peanut-containing foods.

BACKGROUND: Bioaccessibility of food allergens may be a key determinant of allergic reactions. OBJECTIVE: To develop a protocol allowing the detection of the major peanut allergen, Ara h 6, in the bloodstream following ingestion of low amounts of peanut and to compare Ara h 6 bioaccessibility by food matrix. We further assessed for differences in absorption in healthy versus peanut-allergic volunteers. METHODS: A blood pretreatment combining acidic shock and thermal treatment was developed. This protocol was then applied to blood samples collected from human volunteers (n = 6, healthy controls; n = 14, peanut-allergic patients) at various time-points following ingestion of increasing levels of peanut incurred in different food matrices (cookies, peanut butter and chocolate dessert). Immunodetection was performed using an in-house immunoassay. RESULTS: An original pretreatment protocol was optimized, resulting in irreversible dissociation of human antibodies-Ara h 6 immune complex, thus rendering Ara h 6 accessible for its immunodetection. Ara h 6 was detected in samples from all volunteers following ingestion of 300-1000 mg peanut protein, although variations in the kinetics of passage were observed between individuals and matrices. Interestingly, in peanut-allergic subjects, Ara h 6 could be detected following ingestion of lower doses and at higher concentrations than in non-allergic volunteers. CONCLUSIONS AND CLINICAL RELEVANCE: The kinetics and intensity of Ara h 6 passage in bloodstream depend on both individual and food matrix. Peanut-allergic patients appear to demonstrate higher absorption rate, the clinical significance of which warrants further evaluation.

Breastfeeding initiation or duration and longitudinal patterns of infections up to 2 years and skin rash and respiratory symptoms up to 8 years in the EDEN mother-child cohort.

This paper aimed to examine the effect of breastfeeding on longitudinal patterns of common infections up to 2 years and respiratory symptoms up to 8 years. To assess the incidence and reoccurrence of infections and allergic symptoms in the first years of life among 1,603 children from the EDEN mother-child cohort, distinct longitudinal patterns of infectious diseases as well as skin rash and respiratory symptoms were identified by group-based trajectory modelling. To characterize infections, we considered the parent-reported number of cold/nasopharyngitis and diarrhoea from birth to 12 months and otitis and bronchitis/bronchiolitis from birth to 2 years. To characterize allergy-related symptoms, we considered the parent-reported occurrence of wheezing and skin rash from 8 months to 8 years and asthma from 2 to 8 years. Then associations between breastfeeding and these longitudinal patterns were assessed through adjusted multinomial logistic regression. Compared with never-breastfed infants, ever-breastfed infants were at a lower risk of diarrhoea events in early infancy as well as infrequent events of bronchitis/bronchiolitis throughout infancy. Only predominant breastfeeding duration was related to frequent events of bronchitis/bronchiolitis and infrequent events of otitis. We found no significant protective effect of breastfeeding on longitudinal patterns of cold/nasopharyngitis, skin rash, or respiratory symptoms. For an infant population with a short breastfeeding duration, on average, our study confirmed a protective effect of breastfeeding on diarrhoea events in early infancy, infrequent bronchitis/bronchiolitis and, to a lesser extent, infrequent otitis events up to 2 years but not on other infections, skin rash, or respiratory symptoms4.

Variable IgE cross-reactivity between peanut 2S-albumins: The case for measuring IgE to both Ara h 2 and Ara h 6.

BACKGROUND: 2S-albumins Ara h 2 and Ara h 6 are the most potent peanut allergens and levels of specific immunoglobulin E (IgE) towards these proteins are good predictors of clinical reactivity. Because of structural homologies, Ara h 6 is generally considered to cross-react extensively with Ara h 2. OBJECTIVE: We aimed to quantify the IgE cross-reactivity between Ara h 2 and Ara h 6. METHODS: Peanut 2S-albumins were purified from raw peanuts. The IgE cross-reactivity between Ara h 2 and Ara h 6 was evaluated with 32 sera from French and US peanut-allergic patients by measuring the residual IgE-binding to one 2S-albumin after depletion of IgE antibodies recognizing the other 2S-albumin. The IgE cross-reactivity between Ara h 2 and Ara h 6 was further investigated by competitive inhibition of IgE-binding and by a model of mast cell degranulation. RESULTS: A highly variable level of IgE cross-reactivity was revealed among the patients. The mean fraction of cross-reactive IgE antibodies represented only 17.1% of 2S-albumins-specific IgE antibodies and was lower than the mean fraction of IgE specific to Ara h 2 (57.4%) or to Ara h 6 (25.5%). The higher level of Ara h 2-specific IgE was principally due to the IgE-binding capacity of an insertion containing the repeated immunodominant linear epitope DPYSPOH S. The impact of IgE cross-reactivity on diagnostic testing was illustrated with a serum displaying an Ara h 6-specific IgE response of 26 UI/mL that was not associated with the capacity of Ara h 6 to trigger mast cell degranulation. CONCLUSIONS & CLINICAL RELEVANCE: Immunoglobulin E antibodies specific to peanut 2S-albumins are mainly non-cross-reactive, but low-affinity cross-reactivity can affect diagnostic accuracy. Testing IgE-binding to a mixture of 2S-albumins rather than to each separately may enhance diagnostic performance.

EAACI position paper: Influence of dietary fatty acids on asthma, food allergy, and atopic dermatitis.

The prevalence of allergic diseases such as allergic rhinitis, asthma, food allergy, and atopic dermatitis has increased dramatically during the last decades, which is associated with altered environmental exposures and lifestyle practices. The purpose of this review was to highlight the potential role for dietary fatty acids, in the prevention and management of these disorders. In addition to their nutritive value, fatty acids have important immunoregulatory effects. Fatty acid-associated biological mechanisms, human epidemiology, and intervention studies are summarized in this review. The influence of genetics and the microbiome on fatty acid metabolism is also discussed. Despite critical gaps in our current knowledge, it is increasingly apparent that dietary intake of fatty acids may influence the development of inflammatory and tolerogenic immune responses. However, the lack of standardized formats (ie, food versus supplement) and standardized doses, and frequently a lack of prestudy serum fatty acid level assessments in clinical studies significantly limit our ability to compare allergy outcomes across studies and to provide clear recommendations at this time. Future studies must address these limitations and individualized medical approaches should consider the inclusion of specific dietary factors for the prevention and management of asthma, food allergy, and atopic dermatitis.

Evaluation of the efficiency of hydrolyzed whey formula to prevent cow's milk allergy in the BALB/c mouse model.

BACKGROUND: Partially hydrolyzed milk formulas have been proposed for primary prevention in at-risk infants, but evidence of their efficiency and elucidation of the underlying mechanisms are still lacking. Thanks to a Th2-biased mouse model mimicking at-risk patients, we aimed to assess the potency of a partially hydrolyzed whey formula (pHWF) to induce oral tolerance thus preventing further cow's milk (CM) allergy. METHODS: BALB/c mice were gavaged with pHWF, standard milk formula (SF), or vehicle only (PBS+). All mice were then orally sensitized to CM using cholera toxin and further chronically exposed to CM. Humoral (IgE, IgG1, IgG2a) and cellular (Th2/Th1/Th17 cytokine secretion; frequency of CD4+GATA3+ and CD4+CD25+Foxp3+ T cells in the spleen) responses against ß-lactoglobulin (BLG) and whole caseins (CAS) were assessed, as well as a marker of elicitation of allergic reaction (mMCP-1) released after an oral challenge with CM. RESULTS: All markers of sensitization and of allergic reaction were evidenced in the PBS+ mice and were significantly enhanced upon chronic exposure. Gavage with SF totally and durably prevented sensitization and elicitation of the allergic reaction. Conversely, pre-treatment with pHWF only reduced BLG-specific sensitization (IgE, Th2 cytokines), with no significant effect on sensitization to caseins. However, pHWF pre-treatment significantly reduced mMCP-1 concentration in plasma after CM challenges. CD4+CD25+Foxp3+ Treg cell frequency could not be correlated with tolerance efficiency. CONCLUSION: Partially hydrolyzed whey formula only partially prevents the further development of CM allergy in this Th2-biased model. A hydrolysate from both whey and casein fractions may be more efficient.

Immune components of early breastmilk: Association with maternal factors and with reported food allergy in childhood.

BACKGROUND: Breastmilk (BM) may participate in driving gut barrier function and immunity in the neonate. We analyzed immune and growth factor concentrations in early BM and their association with maternal/environmental characteristics and with food allergy (FA) in childhood. METHODS: One BM sample was collected in maternity from some mothers in the EDEN birth cohort (n = 2002 mother-child dyads). A random selection was performed among available samples (subcohort, n = 272), for which all deliveries were full-term, various maternal/environmental characteristics were recorded, and parents answered yearly the question "Has a medical doctor diagnosed a FA in your child?" (26 parent-reported FA cases). Only samples collected between day 2 and day 6 post-partum were considered for descriptive analysis (n = 263). Samples for all other FA cases available were added to the subcohort (46 additional cases; "casecohort" design). Fifty cytokines, antibodies, and growth factor concentrations were determined using multiplexed kits and analyzed using robust statistical procedures. RESULTS: BM components exhibited wide concentration ranges and global day-to-day variation. Different clusters of correlated factors appeared, with components from the main cluster related to maternal diet during pregnancy. Primiparity was positively associated with eleven other components, whereas other factors (eg, maternal atopy and smoking) were related to fewer components. Finally, the casecohort design highlighted a positive association between CXCL10, TNFß, and IL-2 concentrations and reported FA in childhood. CONCLUSION: Beyond the unique description of early BM composition, we show that immune information transmitted to the neonate is related to various maternal factors and identified components associated with FA diagnosis in childhood.

Use of partially hydrolysed formula in infancy and incidence of eczema, respiratory symptoms or food allergies in toddlers from the ELFE cohort.

BACKGROUND AND OBJECTIVES: Partially hydrolyzed formulas (pHF) are recommended in non-breastfed infants with familial history of allergy to prevent allergy development. However, recent meta-analysis does not provide strong support for their protective effect. The present work assesses the links between 2-month infant formula use and the incidence of eczema, respiratory symptoms, or food allergies (FA) up to 2 years of age. METHODS: The nationwide ELFE birth cohort is a population-based study from mainland France. Infant feeding (breast milk only, partially hydrolyzed formula with [pHF-HA] or without a hypoallergenic label [pHF-non-HA], and non-hydrolyzed formula [Nhf]) was reported at 2 months. Eczema, FA, and respiratory symptoms such as wheezing and asthma were reported at 2 months, 1 year, and 2 years. Infants with prior FA at 2 months were excluded from analyses. RESULTS: Among 11 720 infants, those who received only breast milk at 2 months were at lower risk of eczema at 1 year than those who received nHF (OR[95% CI] = 0.78[0.65-0.94] in non-at-risk infants; 0.86[0.75-0.98] in at-risk infants). The use of pHF-HA, compared with nHF, at 2 months was related to higher risk of wheezing at 1 year in at-risk infants (1.68[1.24-2.28]) and higher risk of FA at 2 years both in non-at-risk infants (3.78[1.52-9.41]) and in at-risk infants (2.31[1.36-3.94]). CONCLUSIONS: In this nationwide study, pHF-HA use was not associated with a lower risk of any of the studied outcomes. Quite the reverse, it was associated with a higher risk of wheezing and FA. This should be confirmed in further studies.

Humoral and cellular immune response in Wistar Han RCC rats fed two genetically modified maize MON810 varieties for 90 days (EU 7th Framework Programme project GRACE).

The genetically modified maize event MON810 expresses a Bacillus thuringiensis-derived gene, which encodes the insecticidal protein Cry1Ab to control some lepidopteran insect pests such as the European corn borer. It has been claimed that the immune system may be affected following the oral/intragastric administration of the MON810 maize in various different animal species. In the frame of the EU-funded project GRACE, two 90-day feeding trials, the so-called studies D and E, were performed to analyze the humoral and cellular immune responses of male and female Wistar Han RCC rats fed the MON810 maize. A MON810 maize variety of Monsanto was used in the study D and a MON810 maize variety of Pioneer Hi-Bred was used in the study E. The total as well as the maize protein- and Cry1Ab-serum-specific IgG, IgM, IgA and IgE levels, the proliferative activity of the lymphocytes, the phagocytic activity of the granulocytes and monocytes, the respiratory burst of the phagocytes, a phenotypic analysis of spleen, thymus and lymph node cells as well as the in vitro production of cytokines by spleen cells were analyzed. No specific Cry1Ab immune response was observed in MON810 rats, and anti-maize protein antibody responses were similar in MON810 and control rats. Single parameters were sporadically altered in rats fed the MON810 maize when compared to control rats, but these alterations are considered to be of no immunotoxicological significance.

One-year oral toxicity study on a genetically modified maize MON810 variety in Wistar Han RCC rats (EU 7th Framework Programme project GRACE).

The GRACE (GMO Risk Assessment and Communication of Evidence; www.grace-fp7.eu ) project was funded by the European Commission within the 7th Framework Programme. A key objective of GRACE was to conduct 90-day animal feeding trials, animal studies with an extended time frame as well as analytical, in vitro and in silico studies on genetically modified (GM) maize in order to comparatively evaluate their use in GM plant risk assessment. In the present study, the results of a 1-year feeding trial with a GM maize MON810 variety, its near-isogenic non-GM comparator and an additional conventional maize variety are presented. The feeding trials were performed by taking into account the guidance for such studies published by the EFSA Scientific Committee in 2011 and the OECD Test Guideline 452. The results obtained show that the MON810 maize at a level of up to 33 % in the diet did not induce adverse effects in male and female Wistar Han RCC rats after a chronic exposure.