0
selected
-
1.
Free Amino Acids in Human Milk: A Potential Role for Glutamine and Glutamate in the Protection Against Neonatal Allergies and Infections.
van Sadelhoff, JHJ, Wiertsema, SP, Garssen, J, Hogenkamp, A
Frontiers in immunology. 2020;:1007
Abstract
Breastfeeding is indicated to support neonatal immune development and to protect against neonatal infections and allergies. Human milk composition is widely studied in relation to these unique abilities, which has led to the identification of various immunomodulating components in human milk, including various bioactive proteins. In addition to proteins, human milk contains free amino acids (FAAs), which have not been well-studied. Of those, the FAAs glutamate and glutamine are by far the most abundant. Levels of these FAAs in human milk sharply increase during the first months of lactation, in contrast to most other FAAs. These unique dynamics are globally consistent, suggesting that their levels in human milk are tightly regulated throughout lactation and, consequently, that they might have specific roles in the developing neonate. Interestingly, free glutamine and glutamate are reported to exhibit immunomodulating capacities, indicating that these FAAs could contribute to neonatal immune development and to the unique protective effects of breastfeeding. This review describes the current understanding of the FAA composition in human milk. Moreover, it provides an overview of the effects of free glutamine and glutamate on immune parameters relevant for allergic sensitization and infections in early life. The data reviewed provide rationale to study the role of free glutamine and glutamate in human milk in the protection against neonatal allergies and infections.
-
2.
Pegvaliase: Immunological profile and recommendations for the clinical management of hypersensitivity reactions in patients with phenylketonuria treated with this enzyme substitution therapy.
Hausmann, O, Daha, M, Longo, N, Knol, E, Müller, I, Northrup, H, Brockow, K
Molecular genetics and metabolism. 2019;(1-2):84-91
Abstract
OBJECTIVE To provide recommendations for managing hypersensitivity adverse events (HAEs) to an injectable enzyme substitution therapy (pegvaliase, a PEGylated phenylalanine ammonia lyase enzyme) in adult patients with phenylketonuria (PKU). METHODS Eight European academic immunology experts with a broad range of experience in hypersensitivity, anaphylaxis, and/or drug reactions, and two geneticists from the USA with pegvaliase experience convened for two advisory board meetings. Efficacy, safety, and immunological profile of pegvaliase were discussed with the objective of developing recommendations for the clinical management of HAEs associated with pegvaliase treatment. RESULTS Based on available immunogenicity data, it was concluded that pegvaliase induces a Type III hypersensitivity reaction, causing HAEs with peak event rates during induction/titration and a decline over time during maintenance therapy. The decline in HAEs with longer duration of therapy was considered to likely be driven by anti-drug antibody affinity maturation, reduced immune complex formation, and decreased complement activation over time. Immunology and PKU experts unanimously supported that the use of an induction, titration, and maintenance dosing regimen and implementation of several risk mitigation strategies contributed to the improvement of tolerability over time. Key risk mitigation strategies utilized in the Phase 3 clinical trials such as premedication with H1-receptor antagonists, allowance for a longer titration period after an HAE, patient education, and requirement to carry auto-injectable adrenaline (epinephrine) should be continued in clinical practice. A tool for administration of auto-injectable adrenaline in patients using pegvaliase was suggested. It was added that after the occurrence of a severe HAE a temporary dose reduction is more likely to improve tolerability than treatment interruption. CONCLUSIONS Overall, it was agreed that pegvaliase has a generally tolerable safety profile in adults with PKU. Importantly, the risk mitigation strategies utilized in the clinical trials were considered to support the continued use of key strategies for management in the commercial setting, such as a slow induction/titration dosing paradigm and premedication with H1-receptor antagonists. However, physicians and patients need to be aware of the risk of HAEs associated with pegvaliase; presence of a trained observer during early treatment may be beneficial in certain circumstances, and a requirement to carry auto-injectable adrenaline is recommended. Because pegvaliase offers the possibility to normalize diet, while maintaining blood phenylalanine within the recommended therapeutic range, safe use of this medication in the clinical setting is important. Ongoing monitoring of long-term clinical safety of patients on pegvaliase treatment in the commercial setting was recommended.
-
3.
Factors influencing the infant gut microbiome at age 3-6 months: Findings from the ethnically diverse Vitamin D Antenatal Asthma Reduction Trial (VDAART).
Sordillo, JE, Zhou, Y, McGeachie, MJ, Ziniti, J, Lange, N, Laranjo, N, Savage, JR, Carey, V, O'Connor, G, Sandel, M, et al
The Journal of allergy and clinical immunology. 2017;(2):482-491.e14
-
-
Free full text
-
Abstract
BACKGROUND The gut microbiome in infancy influences immune system maturation, and may have an important impact on allergic disease risk. OBJECTIVE We sought to determine how prenatal and early life factors impact the gut microbiome in a relatively large, ethnically diverse study population of infants at age 3 to 6 months, who were enrolled in Vitamin D Antenatal Asthma Reduction Trial, a clinical trial of vitamin D supplementation in pregnancy to prevent asthma and allergies in offspring. METHODS We performed 16S rRNA gene sequencing on 333 infants' stool samples. Microbial diversity was computed using the Shannon index. Factor analysis applied to the top 25 most abundant taxa revealed 4 underlying bacterial coabundance groups; the first dominated by Firmicutes (Lachnospiraceae/Clostridiales), the second by Proteobacteria (Klebsiella/Enterobacter), the third by Bacteriodetes, and the fourth by Veillonella. Scores for coabundance groups were used as outcomes in regression models, with prenatal/birth and demographic characteristics as independent predictors. Multivariate analysis, using all microbial community members, was also conducted. RESULTS White race/ethnicity was associated with lower diversity but higher Bacteroidetes coabundance scores. C-section birth was associated with higher diversity, but decreased Bacteroidetes coabundance scores. Firmicutes scores were higher for infants born by C-section. Breast-fed infants had lower proportions of Clostridiales. Cord blood vitamin D was linked to increased Lachnobacterium, but decreased Lactococcus. CONCLUSIONS The findings presented here suggest that race, mode of delivery, breast-feeding, and cord blood vitamin D levels are associated with infant gut microbiome composition, with possible long-term implications for immune system modulation and asthma/allergic disease incidence.
-
4.
Effect of Maternal Dietary Patterns during Pregnancy on Self-Reported Allergic Diseases in the First 3 Years of Life: Results from the GUSTO Study.
Loo, EXL, Ong, L, Goh, A, Chia, AR, Teoh, OH, Colega, MT, Chan, YH, Saw, SM, Kwek, K, Gluckman, PD, et al
International archives of allergy and immunology. 2017;(2):105-113
-
-
Free full text
-
Abstract
BACKGROUND Maternal diet during pregnancy has been suggested to be an important early-life exposure that influences immune tolerance and the development of allergic diseases in offspring. METHODS We examined the relationship between maternal dietary patterns assessed using 24-h recalls and food diaries at 26-28 weeks of pregnancy and the subsequent development of allergic outcomes in the offspring in the Growing Up in Singapore towards Healthy Outcomes (GUSTO) birth cohort. Exploratory factor analysis was used to characterize maternal dietary patterns during pregnancy. During repeated visits in the first 36 months of life, questionnaires were administered to ascertain allergic symptoms, namely, eczema, rhinitis, and wheeze. At ages 18 and 36 months, we administered skin-prick testing to inhalant and food allergens. RESULTS Of the 3 maternal dietary patterns that emerged, the seafood and noodles pattern was associated with a reduced risk of developing allergen sensitization at both 18 months (odds ratio [95% confidence interval]: 0.7 [0.5-0.9]) and 36 months (0.7 [0.6-0.9]) after adjustment for a family history of allergy, and ethnicity, sex, and maternal education levels. No associations between the patterns vegetables, fruit, and white rice or pasta, cheese, and processed meat were observed with any of the allergic outcomes in the first 18 and 36 months of life. CONCLUSION Maternal diet during pregnancy can influence the subsequent development of allergic outcomes in offspring.