1.
Precision medicine in cow's milk allergy.
D'Auria, E, Venter, C
Current opinion in allergy and clinical immunology. 2020;(3):233-241
Abstract
PURPOSE OF REVIEW The aim of this review is to describe the role of precision medicine in the diagnosis, treatment, and monitoring of cow's milk allergy. RECENT FINDINGS The development of 'omics' sciences in the field of food allergy has led to a better understanding of the allergenicity of cow's milk proteins and significant advances in the knowledge of the pathogenesis and mechanisms of cow's milk allergy. Omics-based technologies allow the practitioner to better differentiate cow's milk allergy subtypes and to predict cow's milk allergy (CMA) persistence over time. Precision medicine extends the role of the oral food challenge, to determine the individual's threshold doses, and to establish tolerance to baked milk products. Other than symptom relief, dietary strategies are currently being investigated for the potential to induce tolerance. Oral immunotherapy offers a treatment option for patients with severe and persistent IgE-mediated CMA. Individual baseline-immune profiles may be predictive of cow's milk oral immunotherapy safety and efficacy.Patient data derived from current technology, in combination with the patient's history, can be translated into treatments targeted at patient-tailored interventions. SUMMARY The identification of novel biomarkers may improve diagnostic accuracy and also predict patient responsiveness to treatments. Integration of patient data will become increasingly important as omics technologies become more widely used in the clinical setting.
2.
Transforming growth factor beta in human milk and allergic outcomes in children: A systematic review.
Khaleva, E, Gridneva, Z, Geddes, DT, Oddy, WH, Colicino, S, Blyuss, O, Boyle, RJ, Warner, JO, Munblit, D
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2019;(9):1201-1213
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Abstract
BACKGROUND Human milk (HM) transforming growth factor beta (TGF-β) is critical for inflammation regulation and oral tolerance promotion. Previous reports suggested that variations in HM TGF-β levels are associated with allergic outcomes. OBJECTIVE We undertook a systematic review (PROSPERO 2017 CRD42017069920) to reassess the evidence on the relationships between HM TGF-β and allergic outcomes in children. METHODS Electronic bibliographic databases (MEDLINE, EMBASE and Cochrane Library) were systematically searched. Two independent reviewers screened reference lists, extracted the data and assessed risk of bias using the National Institute for Clinical Excellence methodological checklist. RESULTS A total of 21 studies were identified. Sixteen studies assessed relationships between HM TGF-β and risk of eczema; 14, allergic sensitization; nine, wheezing/asthma; six, food allergy; three, allergic rhinitis/conjunctivitis. Five cohorts (5/18, 28%) reported a protective effect of TGF-β1, while 3 (3/10, 30%) suggested increased risk of allergic outcomes development and 1 (1/10, 10%), a protective effect of TGF-β2 on eczema. Meta-analysis was not possible due to significant heterogeneity in methodology, age of outcome assessment and differing statistical approaches. 71% (15/21) of studies carried a high risk of bias. CONCLUSION AND CLINICAL RELEVANCE In contrast with previous findings, we did not find strong evidence of associations between HM TGF-β and allergic outcomes. Differences in studies' methodology and outcomes do not allow unconditional rejection or acceptance of the hypothesis that HM TGF-β influences the risk of allergy development. Future studies on diverse populations employing standardized methods, accurate phenotyping of outcomes and evaluation of the effect of TGF-β in combination with other HM immune markers, microbiome and oligosaccharides are required.
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[Advances in the knowledge about human milk proteins].
Brunser, O
Revista chilena de pediatria. 2018;(2):261-269
Abstract
The mammary gland and maternal milk are the product of millions of years of evolution that resul ted in an optimal composition that sustains the growth and development of newborns and infants. Maternal milk supports the growth, adaptation and survival of this immature organism. Recent studies have detected 1606 different proteins in human milk, most of them synthesized in the acini of the glandular tissue while others originate from distant organs such as the lymphoid tissue and the digestive tract. Maternal milk enzymes modify its proteins and liberate peptides with antimicrobial, antihypertensive or stimulatory activities. This proteolytic activity occurs at specific sites in peptide chains. To prevent the extemporaneous activation of these proteolytic enzymes, that would result in inflammatory processes, maternal milk also contains inhibitory peptides that together with the stimulatory peptides conform a complex regulatory system. Some enzymes in maternal milk main tain their activity in the gastrointestinal tract of infants and compensate for the decreased activity of digestive tract enzymes in newborns. Thus, the milk enterokynase stimulates the release of pancreatic proteases as it induces the liberation of cholecystokynin/pancreozymin. The bile salt-activated lipase of human milk is activated in the duodenum by the infants' bile salts and partially compensates for the low levels of pancreatic lipase in newborns. These milk enzymes probably contribute to the nutrition of premature infants as they increase the availability of amino acids and peptides in their upper gastrointestinal tract; furthermore, as their intestinal epithelium is more permeable to peptides and partially digested protein this may help induce immune tolerance. The most relevant issues in the physiology and composition of the maternal milk are presented in this review.