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Mechanisms Underlying the Skin-Gut Cross Talk in the Development of IgE-Mediated Food Allergy.
van Splunter, M, Liu, L, van Neerven, RJJ, Wichers, HJ, Hettinga, KA, de Jong, NW
Nutrients. 2020;(12)
Abstract
Immune-globulin E (IgE)-mediated food allergy is characterized by a variety of clinical entities within the gastrointestinal tract, skin and lungs, and systemically as anaphylaxis. The default response to food antigens, which is antigen specific immune tolerance, requires exposure to the antigen and is already initiated during pregnancy. After birth, tolerance is mostly acquired in the gut after oral ingestion of dietary proteins, whilst exposure to these same proteins via the skin, especially when it is inflamed and has a disrupted barrier, can lead to allergic sensitization. The crosstalk between the skin and the gut, which is involved in the induction of food allergy, is still incompletely understood. In this review, we will focus on mechanisms underlying allergic sensitization (to food antigens) via the skin, leading to gastrointestinal inflammation, and the development of IgE-mediated food allergy. Better understanding of these processes will eventually help to develop new preventive and therapeutic strategies in children.
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Approaches and Challenges to Management of Pediatric and Adult Patients With Eosinophilic Esophagitis.
Hirano, I, Furuta, GT
Gastroenterology. 2020;(4):840-851
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Treatment of eosinophilic esophagitis has progressed from elemental formula for children and esophageal dilation for adults to selective exclusion of food triggers and swallowed topical corticosteroids. Management guidelines are available from the American Gastroenterological Association and the Joint Task Force on Allergy Immunology Practice Parameters. We cannot, however, evaluate the efficacy of treatments without a definition of response. We propose a treat-to-target approach, based on symptoms and findings from endoscopy and histology. This approach addresses dissociations between outcomes, such as symptom persistence despite normalization of histologic features and symptom resolution after esophageal dilation despite histologic features of active disease. Eosinophilic esophagitis can now be treated with biologic agents that target specific immune pathways, and findings from prospective trials have indicated that less-restrictive, empiric, elimination diets can be effective and reduce the need for repeated endoscopic assessment of disease activity during food reintroduction. We also discuss eosinophilic esophagitis subtypes, factors associated with disease, and advances in management.
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New Perspectives in Food Allergy.
De Martinis, M, Sirufo, MM, Suppa, M, Ginaldi, L
International journal of molecular sciences. 2020;(4)
Abstract
The improvement of the knowledge of the pathophysiological mechanisms underlying the tolerance and sensitization to food antigens has recently led to a radical change in the clinical approach to food allergies. Epidemiological studies show a global increase in the prevalence of food allergy all over the world and manifestations of food allergy appear increasingly frequent also in elderly subjects. Environmental and nutritional changes have partly changed the epidemiology of allergic reactions to foods and new food allergic syndromes have emerged in recent years. The deepening of the study of the intestinal microbiota has highlighted important mechanisms of immunological adaptation of the mucosal immune system to food antigens, leading to a revolution in the concept of immunological tolerance. As a consequence, new prevention models and innovative therapeutic strategies aimed at a personalized approach to the patient affected by food allergy are emerging. This review focuses on these new perspectives and their practical implications in the management of food allergy, providing an updated view of this complex pathology.
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Effects of Lactobacillus pentosus in Children with Allergen-Sensitized Atopic Dermatitis.
Ahn, SH, Yoon, W, Lee, SY, Shin, HS, Lim, MY, Nam, YD, Yoo, Y
Journal of Korean medical science. 2020;(18):e128
Abstract
BACKGROUND Recent studies have shown that oral administration of probiotics may improve the immune imbalance caused by dysbiosis of the gut microbiome in atopic dermatitis (AD). This study aimed to investigate the clinical and immunological effects of Lactobacillus pentosus in children with mild to moderate AD. METHODS Children aged 2-13 years with AD were randomized to receive either 1.0 × 1010 colony-forming units of L. pentosus or placebo, daily, for 12 weeks. The clinical severity of AD and transepidermal water loss were evaluated. Blood eosinophil counts, serum total immunoglobulin E (IgE), and cytokine levels were measured. The diversity and composition of the gut microbiota were also analyzed. RESULTS Eighty-two children were recruited, and 41 were assigned to the probiotics intervention group. The mean scoring of atopic dermatitis (SCORAD) indices at baseline were 30.4 and 34.3 for the probiotics and placebo groups, respectively. At week 12, the mean indices were 23.6 and 23.1 for the probiotics and placebo groups, respectively. Clinical severity decreased significantly over time in both groups, with no significant difference between the two groups. In both groups, there were no significant differences in cytokine levels, microbial diversity, or the relative abundance of the gut microbiota at week 12 compared with the corresponding baseline values. The mean subjective scores of SCORAD indices after intervention for the probiotics group were significantly lower than those for the placebo group in IgE sensitized AD (P = 0.019). CONCLUSION Our results show improved symptoms in the probiotics and placebo groups, and we could not find additional effects of L. pentosus in AD. However, the mean subjective scores of SCORAD indices for the probiotics group are significantly improved compared with those for the placebo group in allergen-sensitized AD.
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Epithelial-stromal crosstalk and fibrosis in eosinophilic esophagitis.
Muir, AB, Wang, JX, Nakagawa, H
Journal of gastroenterology. 2019;(1):10-18
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Eosinophilic esophagitis (EoE) is a food allergen-induced inflammatory disorder. EoE is increasingly recognized as a cause of swallowing dysfunction, food impaction and esophageal stricture. Inflammation of the esophageal mucosa involves immune cell infiltrate, reactive epithelial changes and fibroblast activation, culminating in robust tissue remodeling toward esophageal fibrosis characterized by excess collagen deposition in the subepithelial lamina propria. Fibrosis contributes to a unique mechanical property of the EoE-affected esophagus that is substantially stiffer than the normal esophagus. There is a great need to better understand the processes behind esophageal fibrosis in order to foster improved diagnostic tools and novel therapeutics for EoE-related esophageal fibrosis. In this review, we discuss the role of esophageal inflammatory microenvironment that promotes esophageal fibrosis, with specific emphasis upon cytokines-mediated functional epithelial-stromal interplays, recruitment and activation of a variety of effector cells, and tissue stiffness. We then explore the current state of clinical methodologies to detect and treat the EoE-related esophageal stricture.
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Solid Food Introduction and the Development of Food Allergies.
Caffarelli, C, Di Mauro, D, Mastrorilli, C, Bottau, P, Cipriani, F, Ricci, G
Nutrients. 2018;(11)
Abstract
The rise of food allergy in childhood, particularly among developed countries, has a significant weight on public health and involves serious implications for patients' quality of life. Even if the mechanisms of food tolerance and the complex interactions between the immune system and environmental factors are still mainly unknown, pediatricians have worldwide implemented preventive measures against allergic diseases. In the last few decades, the prevention of food allergy has tracked various strategies of complementary feeding with a modification of international guidelines from delayed introduction to early weaning. Current evidence shows that complementary foods, including allergenic ones, should be introduced into diet after four months, or even better, following World Health Organization advice, around six months irrespective of risk for allergy of the individual. The introduction of peanut is recommended before 12 months of age among infants affected by severe eczema and/or egg allergy to diminish the occurrence of peanut allergy in countries with high peanut consumption. The introduction of heated egg at 6⁻8 months of age may reduce egg allergy. Infants at high risk of allergy similarly to healthy children should introduce complementary foods taking into account family and cultural preferences.
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Pregnancy modulates the allergen-induced cytokine production differently in allergic and non-allergic women.
Abelius, MS, Jedenfalk, M, Ernerudh, J, Janefjord, C, Berg, G, Matthiesen, L, Jenmalm, MC
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2017;(8):818-824
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BACKGROUND The immunological environment during pregnancy may differ between allergic and non-allergic women. This study investigates the effect of maternal allergy on the allergen-induced cytokine and chemokine levels and whether pregnancy modulates these immune responses differently in allergic and non-allergic women. METHODS The birch-, cat-, phytohemagglutinin- and tetanus toxoid-induced interferon-γ (IFN-γ), interleukin (IL)-4, IL-5, IL-10, IL-13, the T-helper 1 (Th1)-associated chemokine CXCL10 and the Th2-associated chemokine CCL17 levels were quantified in 20 women with allergic symptoms (sensitized, n = 13) and 36 women without allergic symptoms (non-sensitized, n = 30) at gestational weeks 10-12, 15-16, 25, 35 and 2 and 12 months post-partum. RESULTS Birch-, but not cat-induced, IL-5, IL-13 and CCL17 levels were increased during pregnancy as compared to post-partum in the sensitized women with allergic symptoms. In contrast, cat-, but not birch-induced, IL-5 and IL-13 levels were increased during pregnancy as compared to post-partum in the non-sensitized women without allergic symptoms. Furthermore, IFN-γ secretion was increased in the first and decreased in the second and third trimesters in response to birch and decreased in the third trimester in response to cat as compared to post-partum in the non-sensitized women without allergic symptoms. Increased allergen-induced IL-4, IL-5 and IL-13 levels were associated with allergic symptoms and sensitization. CONCLUSIONS Pregnancy had a clear effect on the allergen-induced IL-5, IL-13, CCL17, IFN-γ and CXCL10 production, with distinct enhanced Th2-responses to birch in the allergic group and to cat in the non-allergic group.
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Epicutaneous immunotherapy for the treatment of peanut allergy in children and young adults.
Jones, SM, Sicherer, SH, Burks, AW, Leung, DY, Lindblad, RW, Dawson, P, Henning, AK, Berin, MC, Chiang, D, Vickery, BP, et al
The Journal of allergy and clinical immunology. 2017;(4):1242-1252.e9
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BACKGROUND Peanut allergy is common, life-threatening, and without therapeutic options. We evaluated peanut epicutaneous immunotherapy (EPIT) by using Viaskin Peanut for peanut allergy treatment. OBJECTIVE We sought to evaluate the clinical, safety, and immunologic effects of EPIT for the treatment of peanut allergy. METHODS In this multicenter, double-blind, randomized, placebo-controlled study, 74 participants with peanut allergy (ages 4-25 years) were treated with placebo (n = 25), Viaskin Peanut 100 μg (VP100; n = 24) or Viaskin Peanut 250 μg (VP250; n = 25; DBV Technologies, Montrouge, France). The primary outcome was treatment success after 52 weeks, which was defined as passing a 5044-mg protein oral food challenge or achieving a 10-fold or greater increase in successfully consumed dose from baseline to week 52. Adverse reactions and mechanistic changes were assessed. RESULTS At week 52, treatment success was achieved in 3 (12%) placebo-treated participants, 11 (46%) VP100 participants, and 12 (48%) VP250 participants (P = .005 and P = .003, respectively, compared with placebo; VP100 vs VP250, P = .48). Median change in successfully consumed doses were 0, 43, and 130 mg of protein in the placebo, VP100, and VP250 groups, respectively (placebo vs VP100, P = .014; placebo vs VP250, P = .003). Treatment success was higher among younger children (P = .03; age, 4-11 vs >11 years). Overall, 14.4% of placebo doses and 79.8% of VP100 and VP250 doses resulted in reactions, predominantly local patch-site and mild reactions (P = .003). Increases in peanut-specific IgG4 levels and IgG4/IgE ratios were observed in peanut EPIT-treated participants, along with trends toward reduced basophil activation and peanut-specific TH2 cytokines. CONCLUSIONS Peanut EPIT administration was safe and associated with a modest treatment response after 52 weeks, with the highest responses among younger children. This, when coupled with a high adherence and retention rate and significant changes in immune pathways, supports further investigation of this novel therapy.
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Deciphering the black box of food allergy mechanisms.
Sampath, V, Tupa, D, Graham, MT, Chatila, TA, Spergel, JM, Nadeau, KC
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2017;(1):21-27
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OBJECTIVE To review our current understanding of immunotherapy, the immune mechanisms underlying food allergy, and the methodological advances that are furthering our understanding of the role of immune cells and other molecules in mediating food allergies. DATA SOURCES Literature searches were performed using the following combination of terms: allergy, immunotherapy, food, and mechanisms. Data from randomized clinical studies using state-of-the-art mechanistic tools were prioritized. STUDY SELECTIONS Articles were selected based on their relevance to food allergy. RESULTS Current standard of care for food allergies is avoidance of allergenic foods and the use of epinephrine in case of severe reaction during unintentional ingestion. During the last few decades, great strides have been made in understanding the cellular and molecular mechanisms underlying food allergy, and this information is spearheading the development of exciting new treatments. CONCLUSION Immunotherapy protocols are effective in desensitizing individuals to specific allergens; however, recurrence of allergic sensitization is common after discontinuation of therapy. Interestingly, in a subset of individuals, immunotherapy is protective against allergens even after discontinuation of immunotherapy. Whether this protection is permanent is currently unknown because of inadequate long-term follow-up data. Research on understanding the underlying mechanisms may assist in modifying protocols to improve outcome and enable sustained unresponsiveness, rather than a temporary relief against food allergies. The cellular changes brought about by immunotherapy are still a black box, but major strides in our understanding are being made at an exciting pace.