Renz, H., Brandtzaeg, P. & Hornef, M. The impact of perinatal immune development on mucosal homeostasis and chronic inflammation. Nat. Rev. Immunol. 12, 9–23 (2011).
Cao, S., Feehley, T. J. & Nagler, C. R. The role of commensal bacteria in the regulation of sensitization to food allergens. FEBS Lett. 588, 4258–4266 (2014).
Azad, M. B. et al. Infant gut microbiota and food sensitization. Associations in the first year of life. Clin. Exp. Allergy 45, 632–643 (2015).
Ling, Z. et al. Altered fecal microbiota composition associated with food allergy in infants. Appl. Environ. Microbiol. 80, 2546–2554 (2014).
Chen, C.-C., Chen, K.-J., Kong, M.-S., Chang, H.-J. & Huang, J.-L. Alterations in the gut microbiotas of children with food sensitization in early life. Pediatr. Allergy Immunol. 27, 254–262 (2016).
Hamilton, R. G. & Kleine-Tebbe, J. Molecular allergy diagnostics: analytical features that support clinical decisions. Curr. Allergy Asthma Rep. 15, 57 (2015).
Hoffmann, H. J. et al. The clinical utility of basophil activation testing in diagnosis and monitoring of allergic disease. Allergy 70, 1393–1405 (2015).
Santos, A. F. et al. Distinct parameters of the basophil activation test reflect the severity and threshold of allergic reactions to peanut. J. Allergy Clin. Immunol. 135, 179–186 (2015).
Dos Santos, A. F., Cristiano, R., Athayde-Filho, P. F. & Bortoluzzi, A. J. 2-(5-Methyl-1,3,4-oxa-diazol-2-yl)phenyl acetate. Acta Crystallogr. Sect. E Struct. Rep. Online 70, o559 (2014).
Santos, A. F. et al. Basophil activation test discriminates between allergy and tolerance in peanut-sensitized children. J. Allergy Clin. Immunol. 134, 645–652 (2014).
Elizur, A. & Katz, Y. Timing of allergen exposure and the development of food allergy. Treating before the horse is out of the barn. Curr. Opin. Allergy Clin. Immunol. 16, 157–164 (2016).
Osborne, N. J. et al. Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants. J. Allergy Clin. Immunol. 127, 668–676.e2 (2011).
Basera, W. et al. The South African Food Sensitisation and Food Allergy population-based study of IgE-mediated food allergy. Validity, safety, and acceptability. Ann. Allergy Asthma Immunol. 115, 113–119 (2015).
Chen, J., Hu, Y., Allen, K. J., Ho, M. H. K. & Li, H. The prevalence of food allergy in infants in Chongqing. China. Pediatr. Allergy Immunol. 22, 356–360 (2011).
Xepapadaki, P. et al. Incidence and natural history of hen's egg allergy in the first 2 years of life-the EuroPrevall birth cohort study. Allergy 71, 350–357 (2016).
Kelleher, M. M. et al. Skin barrier impairment at birth predicts food allergy at 2 years of age. J. Allergy Clin. Immunol. 137, 1111–1116.e1-8 (2016). This study emphasizes the importance of skin barrier impairment as a possible entry for allergens that trigger transcutaneous sensitization.
Jones, S. M. & Burks, A. W. Food allergy. N. Engl. J. Med. 377, 1168–1176 (2017).
Wood, R. A. et al. Anaphylaxis in America. the prevalence and characteristics of anaphylaxis in the United States. J. Allergy Clin. Immunol. 133, 461–467 (2014).
Turner, P. J. & Campbell, D. E. Epidemiology of severe anaphylaxis. Can we use population-based data to understand anaphylaxis? Curr. Opin. Allergy Clin. Immunol. 16, 441–450 (2016).
Allen, K. & Koplin, J. J. in Food Allergy: Adverse Reactions to Foods and Food Additives 5th edn (eds Metcalfe, D. D., Sampson, H. A., Simon, R. A. & Lack, G.) 121–133 (Wiley-Blackwell, 2014).
Prescott, S. L. et al. A global survey of changing patterns of food allergy burden in children. World Allergy Organiz. J. 6, 21 (2013). This is the most comprehensive survey of global changes in food allergy burden in children.
National Academies of Sciences, Engineering, and Medicine. Finding a Path to Safety in Food Allergy: Assessment of the Global Burden, Causes, Prevention, Management, and Public Policy. (The National Academies Press, 2016)
Jo, J., Garssen, J., Knippels, L. & Sandalova, E. Role of cellular immunity in cow's milk allergy. Pathogenesis, tolerance induction, and beyond. Mediators Inflamm. 2014, 249784 (2014).
Schoemaker, A. A. et al. Incidence and natural history of challenge-proven cow's milk allergy in European children — EuroPrevall birth cohort. Allergy 70, 963–972 (2015).
Peters, R. L. et al. Natural history of peanut allergy and predictors of resolution in the first 4 years of life. A population-based assessment. J. Allergy Clin. Immunol. 135, 1257–1266.e2 (2015).
Gounni, A. S. et al. High-affinity IgE receptor on eosinophils is involved in defence against parasites. Nature 367, 183–186 (1994).
Noval Rivas, M. & Chatila, T. A. Regulatory T cells in allergic diseases. J. Allergy Clin. Immunol. 138, 639–652 (2016).
Perrier, C. & Corthesy, B. Gut permeability and food allergies. Clin. Exp. Allergy 41, 20–28 (2011).
Williams, K. W. & Sharma, H. P. Anaphylaxis and urticaria. Immunol. Allergy Clin. North Am. 35, 199–219 (2015).
Khan, B. Q. & Kemp, S. F. Pathophysiology of anaphylaxis. Curr. Opin. Allergy Clin. Immunol. 11, 319–325 (2011).
Pushparaj, P. N. et al. The cytokine interleukin-33 mediates anaphylactic shock. Proc. Natl Acad. Sci. USA 106, 9773–9778 (2009).
Burton, O. T. et al. Direct effects of IL-4 on mast cells drive their intestinal expansion and increase susceptibility to anaphylaxis in a murine model of food allergy. Mucosal Immunol. 6, 740–750 (2013).
Gri, G. et al. CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction. Immunity 29, 771–781 (2008).
Noval Rivas, M. et al. Regulatory T cell reprogramming toward a TH2-cell-like lineage impairs oral tolerance and promotes food allergy. Immunity 42, 512–523 (2015). Oral tolerance is another important programme of immune regulation against food antigens. In this paper, the important role of Treg cells is delineated.
Vadas, P. et al. Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis. N. Engl. J. Med. 358, 28–35 (2008).
Tordesillas, L., Rahman, A. H., Hartmann, B. M., Sampson, H. A. & Berin, M. C. Mass cytometry profiling the response of basophils and the complete peripheral blood compartment to peanut. J. Allergy Clin. Immunol. 138, 1741–1744.e9 (2016).
Asero, R. et al. EpidemAAITO: features of food allergy in Italian adults attending allergy clinics: a multi-centre study. Clin. Exp. Allergy 39, 547–555 (2009).
Platts-Mills, T. A. E., Schuyler, A. J., Tripathi, A. & Commins, S. P. Anaphylaxis to the carbohydrate side chain alpha-gal. Immunol. Allergy Clin. North Amer. 35, 247–260 (2015).
Wilson, J. M., Schuyler, A. J., Schroeder, N. & Platts-Mills, Galactose, T. A. E.-α-1,3-Galactose. atypical food allergen or model IgE hypersensitivity? Curr. Allergy Asthma Rep. 17, 8 (2017).
Commins, S. P. & Platts-Mills, T. A. E. Tick bites and red meat allergy. Curr. Opin. Allergy Clin. Immunol. 13, 354–359 (2013).
Oettgen, H. C. et al. Active anaphylaxis in IgE-deficient mice. Nature 370, 367–370 (1994).
Finkelman, F. D. Anaphylaxis. Lessons from mouse models. J. Allergy Clin. Immunol. 120, 506–517 (2007).
Leung, D. Y. M. et al. Effect of anti-IgE therapy in patients with peanut allergy. N. Engl. J. Med. 348, 986–993 (2003). This is a key study demonstrating the benefit of pharmacotherapy directed against TH2-dependent immune pathways (in this case, anti-IgE) to modulate food allergy.
Brandt, E. B. et al. Mast cells are required for experimental oral allergen-induced diarrhea. J. Clin. Invest. 112, 1666–1677 (2003).
Mathias, C. B. et al. IgE-mediated systemic anaphylaxis and impaired tolerance to food antigens in mice with enhanced IL-4 receptor signaling. J. Allergy Clin. Immunol. 127, 795–805.e1-6 (2011).
Sampson, H. A. et al. Food allergy. A practice parameter update-2014. J. Allergy Clin. Immunol. 134, 1016–1025.e43 (2014).
Forbes, E. E. et al. IL-9- and mast cell-mediated intestinal permeability predisposes to oral antigen hypersensitivity. J. Exp. Med. 205, 897–913 (2008).
Chen, C.-Y. et al. Induction of Interleukin-9-producing mucosal mast cells promotes susceptibility to IgE-mediated experimental food allergy. Immunity 43, 788–802 (2015).
Louahed, J. et al. Interleukin-9 upregulates mucus expression in the airways. Am. J. Respiratory Cell. Mol. Biol. 22, 649–656 (2000).
Faulkner, H., Renauld, J. C., van Snick, J. & Grencis, R. K. Interleukin-9 enhances resistance to the intestinal nematode Trichuris muris. Infection Immun. 66, 3832–3840 (1998).
Chang, H.-C. et al. The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation. Nat. Immunol. 11, 527–534 (2010).
Staudt, V. et al. Interferon-regulatory factor 4 is essential for the developmental program of T helper 9 cells. Immunity 33, 192–202 (2010).
Chatila, T. A. Interleukin-4 receptor signaling pathways in asthma pathogenesis. Trends Mol. Med. 10, 493–499 (2004).
Malbec, O. & Daëron, M. The mast cell IgG receptors and their roles in tissue inflammation. Immunol. Rev. 217, 206–221 (2007).
Savilahti, E. M. et al. Early recovery from cow's milk allergy is associated with decreasing IgE and increasing IgG4 binding to cow's milk epitopes. J. Allergy Clin. Immunol. 125, 1315 (2010).
Caubet, J. C. et al. Significance of ovomucoid- and ovalbumin-specific IgE/IgG4 ratios in egg allergy. J. Allergy Clin. Immunol. 129, 739–747 (2012).
Burton, O. T. et al. Oral immunotherapy induces IgG antibodies that act through FcγRIIb to suppress IgE-mediated hypersensitivity. J. Allergy Clin. Immunol. 134, 1310–1317.e6 (2014).
Patil, S. U. et al. Peanut oral immunotherapy transiently expands circulating Ara h 2-specific B cells with a homologous repertoire in unrelated subjects. J. Allergy Clin. Immunol. 136, 125–134.e12 (2015).
Santos, A. F. et al. IgG4 inhibits peanut-induced basophil and mast cell activation in peanut-tolerant children sensitized to peanut major allergens. J. Allergy Clin. Immunol. 135, 1249–1256 (2015).
Uermosi, C. et al. Mechanisms of allergen-specific desensitization. J. Allergy Clin. Immunol. 126, 375–383 (2010).
Holt, P. G. et al. Distinguishing benign from pathologic TH2 immunity in atopic children. J. Allergy Clin. Immunol. 137, 379–387 (2016).
Buhner, S. & Schemann, M. Mast cell-nerve axis with a focus on the human gut. Biochim. Biophys. Acta 1822, 85–92 (2012).
Abraham, S. N. & St John, A. L. Mast cell-orchestrated immunity to pathogens. Nat. Rev. Immunol. 10, 440–452 (2010).
Zogaj, D., Ibranji, A. & Hoxha, M. Exercise-induced anaphylaxis: the role of cofactors. Mater. Sociomed. 26, 401–404 (2014).
Harada, S. et al. Aspirin enhances the induction of type I allergic symptoms when combined with food and exercise in patients with food-dependent exercise-induced anaphylaxis. Br. J. Dermatol. 145, 336–339 (2001).
Bauer, C. S., Kampitak, T., Messieh, M. L., Kelly, K. J. & Vadas, P. Heterogeneity in presentation and treatment of catamenial anaphylaxis. Ann. Allergy Asthma Immunol. 111, 107–111 (2013).
Greenhawt, M., Aceves, S. S., Spergel, J. M. & Rothenberg, M. E. The management of eosinophilic esophagitis. The journal of allergy and clinical immunology. In Practice 1, 332–342 (2013).
Mishra, A., Schlotman, J., Wang, M. & Rothenberg, M. E. Critical role for adaptive T cell immunity in experimental eosinophilic esophagitis in mice. J. Leukoc. Biol. 81, 916–924 (2007).
Foroughi, S. et al. Anti-IgE treatment of eosinophil-associated gastrointestinal disorders. J. Allergy Clin. Immunol. 120, 594–601 (2007).
Rocha, R. et al. Omalizumab in the treatment of eosinophilic esophagitis and food allergy. Eur. J. Pediatr. 170, 1471–1474 (2011).
Clayton, F. et al. Eosinophilic esophagitis in adults is associated with IgG4 and not mediated by IgE. Gastroenterology 147, 602–609 (2014).
Aceves, S. S. et al. Mast cells infiltrate the esophageal smooth muscle in patients with eosinophilic esophagitis, express TGF-β1, and increase esophageal smooth muscle contraction. J. Allergy Clin. Immunol. 126, 1198 (2010).
Blanchard, C. et al. IL-13 involvement in eosinophilic esophagitis. Transcriptome analysis and reversibility with glucocorticoids. J. Allergy Clin. Immunol. 120, 1292–1300 (2007).
Aceves, S. S., Newbury, R. O., Dohil, R., Bastian, J. F. & Broide, D. H. Esophageal remodeling in pediatric eosinophilic esophagitis. J. Allergy Clin. Immunol. 119, 206–212 (2007).
Blanchard, C. et al. Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J. Clin. Invest. 116, 536–547 (2006).
Sherrill, J. D. et al. Variants of thymic stromal lymphopoietin and its receptor associate with eosinophilic esophagitis. J. Allergy Clin. Immunol. 126, 160–165.e3 (2010).
Kottyan, L. C. et al. Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease. Nat. Genet. 46, 895–900 (2014).
Sleiman, P. M. A. et al. GWAS identifies four novel eosinophilic esophagitis loci. Nat. Commun. 5, 5593 (2014).
Litosh, V. A. et al. Calpain-14 and its association with eosinophilic esophagitis. J. Allergy Clin. Immunol. 139, 1762 (2017).
Goldman, H. & Proujansky, R. Allergic proctitis and gastroenteritis in children. Clinical and mucosal biopsy features in 53 cases. Am. J. Surg. Pathol. 10, 75–86 (1986).
Boyce, J. A. et al. Guidelines for the diagnosis and management of food allergy in the United States. Report of the NIAID-sponsored expert panel. J. Allergy Clin. Immunol. 126, S1–58 (2010). This guideline is of clinical relevance for the diagnosis and management of food allergies (in the United States).
Caubet, J.-C., Szajewska, H., Shamir, R. & Nowak Wegrzyn, A. Non-IgE-mediated gastrointestinal food allergies in children. Pediatr. Allergy Immunol. 28, 6–17 (2017).
Berin, M. C. Immunopathophysiology of food protein-induced enterocolitis syndrome. J. Allergy Clin. Immunol. 135, 1108–1113 (2015).
Chinthrajah, R. S., Hernandez, J. D., Boyd, S. D., Galli, S. J. & Nadeau, K. C. Molecular and cellular mechanisms of food allergy and food tolerance. J. Allergy Clin. Immunol. 137, 984–997 (2016).
Cerovic, V., Bain, C. C., Mowat, A. M. & Milling, S. W. F. Intestinal macrophages and dendritic cells. What's the difference? Trends Immunol. 35, 270–277 (2014).
McDole, J. R. et al. Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine. Nature 483, 345–349 (2012).
Hershberg, R. M. et al. Highly polarized HLA class II antigen processing and presentation by human intestinal epithelial cells. J. Clin. Invest. 102, 792–803 (1998).
Rescigno, M. et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol. 2, 361–367 (2001).
Niess, J. H. et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307, 254–258 (2005).
Coombes, J. L. et al. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J. Exp. Med. 204, 1757–1764 (2007).
Iwata, M. et al. Retinoic acid imprints gut-homing specificity on T cells. Immunity 21, 527–538 (2004).
Elias, K. M. et al. Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway. Blood 111, 1013–1020 (2008).
Worthington, J. J., Czajkowska, B. I., Melton, A. C. & Travis, M. A. Intestinal dendritic cells specialize to activate transforming growth factor-β and induce Foxp3+ regulatory T cells via integrin αvβ8. Gastroenterology 141, 1802–1812 (2011).
Boyle, R. J., Hardikar, W. & Tang, M. L. K. The development of food allergy after liver transplantation. Liver Transpl. 11, 326–330 (2005).
Brown, C. et al. High prevalence of food sensitisation in young children with liver disease. A clue to food allergy pathogenesis? Pediatr. Allergy Immunol. 23, 771–778 (2012).
Uematsu, S. et al. Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. Nature Immunol. 9, 769–776 (2008).
Cerovic, V. et al. Hyporesponsiveness of intestinal dendritic cells to TLR stimulation is limited to TLR4. J. Immunol. 182, 2405–2415 (2009).
Laffont, S., Siddiqui, K. R. R. & Powrie, F. Intestinal inflammation abrogates the tolerogenic properties of MLN CD103+ dendritic cells. Eur. J. Immunol. 40, 1877–1883 (2010).
Hammad, H. & Lambrecht, B. N. Barrier epithelial cells and the control of type 2 immunity. Immunity 43, 29–40 (2015). This paper highlights the role of epithelial barrier cells in the control of type 2 immunity. This concept can be applied not only to the respiratory mucosal system but also to the gastrointestinal tract and the cutaneous barrier.
Blazquez, A. B. & Berin, M. C. Gastrointestinal dendritic cells promote TH2 skewing via OX40L. J. Immunol. 180, 4441–4450 (2008).
Noval Rivas, M., Burton, O. T., Oettgen, H. C. & Chatila, T. IL-4 production by group 2 innate lymphoid cells promotes food allergy by blocking regulatory T-cell function. J. Allergy Clin. Immunol. 138, 801–811.e9 (2016).
Burton, O. T. et al. Immunoglobulin E signal inhibition during allergen ingestion leads to reversal of established food allergy and induction of regulatory T cells. Immunity 41, 141–151 (2014).
Brough, H. A. et al. Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy. J. Allergy Clin. Immunol. 135, 164–170 (2015).
Webber, C. M. & England, R. W. Oral allergy syndrome: a clinical, diagnostic, and therapeutic challenge. Ann. Allergy Asthma Immunol. 104, 101–108 (2010).
Benedé, S., Blázquez, A. B., Chiang, D., Tordesillas, L. & Berin, M. C. The rise of food allergy: environmental factors and emerging treatments. EBioMedicine 7, 27–34 (2016).
Stefka, A. T. et al. Commensal bacteria protect against food allergen sensitization. Proc. Natl Acad. Sci. USA 111, 13145–13150 (2014).
Noval Rivas, M. et al. A microbiota signature associated with experimental food allergy promotes allergic sensitization and anaphylaxis. J. Allergy Clin. Immunol. 131, 201–212 (2013).
Atarashi, K. et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331, 337–341 (2011).
Fujimura, K. E. et al. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat. Med. 22, 1187–1191 (2016). This paper highlights the role of the neonatal gut microbiota in promoting the development of allergic sensitization.
Arpaia, N. et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504, 451–455 (2013).
Furusawa, Y. et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446–450 (2013).
Smith, P. M. et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341, 569–573 (2013).
Macia, L. et al. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat. Commun. 6, 6734 (2015).
Kuehn, H. S. & Gilfillan, A. M. G protein-coupled receptors and the modification of FcεRI-mediated mast cell activation. Immunol. Lett. 113, 59–69 (2007).
Dwyer, D. F., Barrett, N. A. & Austen, K. F. Expression profiling of constitutive mast cells reveals a unique identity within the immune system. Nat. Immunol. 17, 878–887 (2016).
McNeil, B. D. et al. Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature 519, 237–241 (2015).
Muraro, A. et al. EAACI food allergy and anaphylaxis guidelines. Diagnosis and management of food allergy. Allergy 69, 1008–1025 (2014).
Venter, C. et al. Better recognition, diagnosis and management of non-IgE-mediated cow's milk allergy in infancy. IMAP-an international interpretation of the MAP (Milk Allergy in Primary Care) guideline. Clin. Transl Allergy 7, 26 (2017).
Sampson, H. A. Food allergy — accurately identifying clinical reactivity. Allergy 60 (Suppl. 79), 19–24 (2005).
Deschildre, A. et al. Food allergy phenotypes. The key to personalized therapy. Clin. Exp. Allergy 47, 1125–1137 (2017).
Sporik, R., Hill, D. J. & Hosking, C. S. Specificity of allergen skin testing in predicting positive open food challenges to milk, egg and peanut in children. Clin. Exp. Allergy 30, 1540–1546 (2000).
Otani, I. M. et al. Multiple-allergen oral immunotherapy improves quality of life in caregivers of food-allergic pediatric subjects. Allergy Asthma Clin. Immunol. 10, 25 (2014).
Wang, J., Godbold, J. H. & Sampson, H. A. Correlation of serum allergy (IgE) tests performed by different assay systems. J. Allergy Clin. Immunol. 121, 1219–1224 (2008).
Sampson, H. A. Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J. Allergy Clin. Immunol. 107, 891–896 (2001).
Garcia-Ara, C. et al. Specific IgE levels in the diagnosis of immediate hypersensitivity to cows’ milk protein in the infant. J. Allergy Clin. Immunol. 107, 185–190 (2001).
Clark, A. T. & Ewan, P. W. Interpretation of tests for nut allergy in one thousand patients, in relation to allergy or tolerance. Clin. Exp. Allergy 33, 1041–1045 (2003).
Perry, T. T., Matsui, E. C., Kay Conover-Walker, M. & Wood, R. A. The relationship of allergen-specific IgE levels and oral food challenge outcome. J. Allergy Clin. Immunol. 114, 144–149 (2004).
Komata, T., Soderstrom, L., Borres, M. P., Tachimoto, H. & Ebisawa, M. The predictive relationship of food-specific serum IgE concentrations to challenge outcomes for egg and milk varies by patient age. J. Allergy Clin. Immunol. 119, 1272–1274 (2007).
Maloney, J. M., Rudengren, M., Ahlstedt, S., Bock, S. A. & Sampson, H. A. The use of serum-specific IgE measurements for the diagnosis of peanut, tree nut, and seed allergy. J. Allergy Clin. Immunol. 122, 145–151 (2008).
Adatia, A. & Clarke, A. E., Yanishevsky, Y. & Ben-Shoshan, M. Sesame allergy: current perspectives. J. Asthma Allergy 10, 141–151 (2017).
Jappe, U. & Schwager, C. Relevance of lipophilic allergens in food allergy diagnosis. Curr. Allergy Asthma Rep. 17, 61 (2017).
Sampson, H. A. et al. Standardizing double-blind, placebo-controlled oral food challenges. American Academy of Allergy, Asthma and Immunology-European Academy of Allergy and Clinical Immunology PRACTALL consensus report. J. Allergy Clin. Immunol. 130, 1260–1274 (2012).
David, T. J., Waddington, E. & Stanton, R. H. Nutritional hazards of elimination diets in children with atopic eczema. Arch. Dis. Child. 59, 323–325 (1984).
Koplin, J. J. & Allen, K. J. Optimal timing for solids introduction — why are the guidelines always changing? Clin. Exp. Allergy 43, 826–834 (2013).
American Academy of Pediatrics. Committee on Nutrition. Hypoallergenic infant formulas. Pediatrics 106, 346–349 (2000).
Koplin, J. J. et al. Can early introduction of egg prevent egg allergy in infants? A population-based study. J. Allergy Clin. Immunol. 126, 807–813 (2010).
Du Toit, G. et al. Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy. J. Allergy Clin. Immunol. 122, 984–991 (2008).
Allen, K. J. & Koplin, J. J. Prospects for prevention of food allergy. J. Allergy Clin. Immunol. Pract. 4, 215–220 (2016).
Lack, G. Epidemiologic risks for food allergy. J. Allergy Clin. Immunol. 121, 1331–1336 (2008).
Weiss, S. T. & Litonjua, A. A. Childhood asthma is a fat-soluble vitamin deficiency disease. Clin. Exp. Allergy 38, 385–387 (2008).
Strachan, D. P. Hay fever, hygiene, and household size. BMJ 299, 1259–1260 (1989). In this paper, the hygiene hypothesis in its original context is reported for the first time.
Lowe, A. J. Prevention of Eczema By a Barrier Lipid Equilibrium Strategy (PEBBLES) pilot study - Testing the compliance and saftey of a strategy for improving infant skin function. Australia New Zealand Clinical Trials Registry https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12609000727246 (2013).
Allen, K. J. et al. VITALITY trial. Protocol for a randomised controlled trial to establish the role of postnatal vitamin D supplementation in infant immune health. BMJ Open 5, e009377 (2015).
Camargo, C. A., Clark, S., Kaplan, M. S., Lieberman, P. & Wood, R. A. Regional differences in EpiPen prescriptions in the United States: the potential role of vitamin D. J. Allergy Clin. Immunol. 120, 131–136 (2007).
Mullins, R. J. & Camargo, C. A. Latitude, sunlight, vitamin D, and childhood food allergy/anaphylaxis. Curr. Allergy Asthma Rep. 12, 64–71 (2012).
Mullins, R. J., Clark, S. & Camargo, C. A. Regional variation in epinephrine autoinjector prescriptions in Australia. More evidence for the vitamin D-anaphylaxis hypothesis. Ann. Allergy Asthma Immunol. 103, 488–495 (2009).
Mullins, R. J. et al. Season of birth and childhood food allergy in Australia. Pediatr. Allergy Immunol. 22, 583–589 (2011).
Vassallo, M. F. et al. Season of birth and food allergy in children. Ann. Allergy Asthma Immunol. 104, 307–313 (2010).
Allen, K. J. et al. Vitamin D insufficiency is associated with challenge-proven food allergy in infants. J. Allergy Clin. Immunol. 131, 1109–1116.e6 (2013). This study associates vitamin D insufficiency with food allergy. The study is particularly important as it was performed in challenge-proven food-allergic infants.
Molloy, J. et al. Is low vitamin D status a risk factor for food allergy? Current evidence and future directions. Mini Rev. Med. Chem. 15, 944–952 (2015).
Julia, V., Macia, L. & Dombrowicz, D. The impact of diet on asthma and allergic diseases. Nat. Rev. Immunol. 15, 308–322 (2015).
Kongsbak, M. et al. Vitamin D up-regulates the vitamin D receptor by protecting it from proteasomal degradation in human CD4+ T cells. PLoS One 9, e96695 (2014).
Wittke, A., Weaver, V., Mahon, B. D., August, A. & Cantorna, M. T. Vitamin D receptor-deficient mice fail to develop experimental allergic asthma. J. Immunol. 173, 3432–3436 (2004).
Renz, H. et al. An exposome perspective. Early-life events and immune development in a changing world. J. Allergy Clin. Immunol. 140, 24–40 (2017).
Ege, M. J. et al. Exposure to environmental microorganisms and childhood asthma. N. Engl. J. Med. 364, 701–709 (2011).
Braun-Fahrländer, C. et al. Environmental exposure to endotoxin and its relation to asthma in school-age children. N. Engl. J. Med. 347, 869–877 (2002). This study associates asthma protection in children living on traditional farms with chronic microbial exposure (measured as endotoxin content in mattress dust as a surrogate marker for Gram-negative bacterial exposure), highlighting the hygiene hypothesis as a concept for allergen prevention.
Green, B. J. et al. Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma. PLoS ONE 9, e100645 (2014).
Renz-Polster, H. et al. Caesarean section delivery and the risk of allergic disorders in childhood. Clin. Exp. Allergy 35, 1466–1472 (2005).
Thavagnanam, S., Fleming, J., Bromley, A., Shields, M. D. & Cardwell, C. R. A meta-analysis of the association between Caesarean section and childhood asthma. Clin. Exp. Allergy 38, 629–633 (2008).
Cardwell, C. R. et al. Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus. A meta-analysis of observational studies. Diabetologia 51, 726–735 (2008).
Koplin, J. J. et al. Environmental and demographic risk factors for egg allergy in a population-based study of infants. Allergy 67, 1415–1422 (2012).
Marrs, T. et al. Is there an association between microbial exposure and food allergy? A systematic review. Pediatr. Allergy Immunol. 24, 311–320.e8 (2013).
Papathoma, E., Triga, M., Fouzas, S. & Dimitriou, G. Cesarean section delivery and development of food allergy and atopic dermatitis in early childhood. Pediatr. Allergy Immunol. 27, 419–424 (2016).
Katz, Y. et al. Early exposure to cow's milk protein is protective against IgE-mediated cow's milk protein allergy. J. Allergy Clin. Immunol. 126, 77–82.e1 (2010).
Du Toit, G. et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N. Engl. J. Med. 372, 803–813 (2015). This hallmark study associates peanut consumption early in life with the prevention of peanut allergy. This study provides the database for new conceptual outreach in the area of food tolerance development.
Koplin, J. J. et al. Understanding the feasibility and implications of implementing early peanut introduction for prevention of peanut allergy. J. Allergy Clin. Immunol. 138, 1131–1141.e2 (2016).
Natsume, O. et al. Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT). A randomised, double-blind, placebo-controlled trial. Lancet 389, 276–286 (2017).
Palmer, D. J. et al. Early regular egg exposure in infants with eczema. A randomized controlled trial. J. Allergy Clin. Immunol. 132, 387–392.e1 (2013).
Palmer, D. J., Sullivan, T. R., Gold, M. S., Prescott, S. L. & Makrides, M. Randomized controlled trial of early regular egg intake to prevent egg allergy. J. Allergy Clin. Immunol. 139, 1600–1607.e2 (2017).
Wei-Liang Tan, J. et al. A randomized trial of egg introduction from 4 months of age in infants at risk for egg allergy. J. Allergy Clin. Immunol. 139, 1621–1628.e8 (2017).
Bellach, J. et al. Randomized placebo-controlled trial of hen's egg consumption for primary prevention in infants. J. Allergy Clin. Immunol. 139, 1591–1599.e2 (2017).
Boyle, R. J. et al. Hydrolysed formula and risk of allergic or autoimmune disease. Systematic review and meta-analysis. BMJ 352, i974 (2016).
National Institute of Allergy and Infectious Diseases (NIAID-Panel). Addendum Guidelines for the Prevention of Peanut Allergy in the United States (National Institute of Allergy and Infectious Diseases, 2017)
Tey, D. et al. Population response to change in infant feeding guidelines for allergy prevention. J. Allergy Clin. Immunol. 133, 476–484 (2014).
Worm, M. et al. Guidelines on the management of IgE-mediated food allergies. S2k-Guidelines of the German Society for Allergology and Clinical Immunology (DGAKI) in collaboration with the German Medical Association of Allergologists (AeDA), the German Professional Association of Pediatricians (BVKJ), the German Allergy and Asthma Association (DAAB), German Dermatological Society (DDG), the German Society for Nutrition (DGE), the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS), the German Society for Oto-Rhino-Laryngology, Head and Neck Surgery, the German Society for Pediatric and Adolescent Medicine (DGKJ), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Society for Pneumology (DGP), the German Society for Pediatric Gastroenterology and Nutrition (GPGE), German Contact Allergy Group (DKG), the Austrian Society for Allergology and Immunology (AE-GAI), German Professional Association of Nutritional Sciences (VDOE) and the Association of the Scientific Medical Societies Germany (AWMF). Allergo J. Int. 24, 256–293 (2015).
Muraro, A. et al. Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology. Allergy 69, 1026–1045 (2014).
Taylor, S. L. & Hefle, S. L. Food allergen labeling in the USA and Europe. Curr. Opin. Allergy Clin. Immunol. 6, 186–190 (2006).
Marchisotto, M. J. et al. Food Allergen Labeling and Purchasing Habits in the United States and Canada. J. Allergy Clin. Immunol. Pract. 5, 345–351.e2 (2017).
Hefle, S. L. & Taylor, S. L. How much food is too much? Threshold doses for allergenic foods. Curr. Allergy Asthma Rep. 2, 63–66 (2002).
Hourihane, J. O. et al. Peanut Allergen Threshold Study (PATS). Novel single-dose oral food challenge study to validate eliciting doses in children with peanut allergy. J. Allergy Clin. Immunol. 139, 1583–1590 (2017).
Trendelenburg, V. et al. Detection of relevant amounts of cow's milk protein in non-pre-packed bakery products sold as cow's milk-free. Allergy 70, 591–597 (2015).
Turner, P. J. et al. Can we identify patients at risk of life-threatening allergic reactions to food? Allergy 71, 1241–1255 (2016).
Brockow, K. et al. Effects of a structured educational intervention on knowledge and emergency management in patients at risk for anaphylaxis. Allergy 70, 227–235 (2015).
Narisety, S. D. et al. A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy. J. Allergy Clin. Immunol. 135, 1275–1282.e6 (2015).
Nurmatov, U. et al. Allergen immunotherapy for IgE-mediated food allergy. A systematic review and meta-analysis. Allergy 72, 1133–1147 (2017).
Beyer, K. A. European perspective on immunotherapy for food allergies. J. Allergy Clin. Immunol. 129, 1179–1184 (2012). This paper emphasizes the European perspective on immune therapy for food allergy.
Jones, S. M. et al. Epicutaneous immunotherapy for the treatment of peanut allergy in children and young adults. J. Allergy Clin. Immunol. 139, 1242–1252.e9 (2017).
Lucendo, A. J., Arias, A. & Tenias, J. M. Relation between eosinophilic esophagitis and oral immunotherapy for food allergy. A systematic review with meta-analysis. Ann. Allergy Asthma Immunol. 113, 624–629 (2014).
Wood, R. A. et al. A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy. J. Allergy Clin. Immunol. 137, 1103–1110.e11 (2016).
MacGinnitie, A. J. et al. Omalizumab facilitates rapid oral desensitization for peanut allergy. J. Allergy Clin. Immunol. 139, 873–881.e8 (2017).
Brandstrom, J. et al. Individually dosed omalizumab. An effective treatment for severe peanut allergy. Clin. Exp. Allergy 47, 540–550 (2017).
Morou, Z., Tatsioni, A., Dimoliatis, I. D. K. & Papadopoulos, N. G. Health-related quality of life in children with food allergy and their parents. A systematic review of the literature. J. Investigat. Allergol. Clin. Immunol. 24, 382–395 (2014).
Avery, N. J., King, R. M., Knight, S. & Hourihane, J. O. Assessment of quality of life in children with peanut allergy. Pediatr. Allergy Immunol. 14, 378–382 (2003).
Flokstra-de Blok, B. M. J. et al. Health-related quality of life of food allergic patients. Comparison with the general population and other diseases. Allergy 65, 238–244 (2010).
Primeau, M. N. et al. The psychological burden of peanut allergy as perceived by adults with peanut allergy and the parents of peanut-allergic children. Clin. Exp. Allergy 30, 1135–1143 (2000).
Salvilla, S. A. et al. Disease-specific health-related quality of life instruments for IgE-mediated food allergy. Allergy 69, 834–844 (2014).
Cohen, B. L., Noone, S., Munoz-Furlong, A. & Sicherer, S. H. Development of a questionnaire to measure quality of life in families with a child with food allergy. J. Allergy Clin. Immunol. 114, 1159–1163 (2004).
Howe, L., Franxman, T., Teich, E. & Greenhawt, M. What affects quality of life among caregivers of food-allergic children? Ann. Allergy Asthma Immunol. 113, 69–74.e2 (2014).
Allen, C. W., Bidarkar, M. S., vanNunen, S. A. & Campbell, D. E. Factors impacting parental burden in food-allergic children. J. Paediatr. Child Health 51, 696–698 (2015).
Ward, C. E. & Greenhawt, M. J. Treatment of allergic reactions and quality of life among caregivers of food-allergic children. Ann. Allergy Asthma Immunol. 114, 312–318.e2 (2015).
Lieberman, J. A., Weiss, C., Furlong, T. J., Sicherer, M. & Sicherer, S. H. Bullying among pediatric patients with food allergy. Ann. Allergy Asthma Immunol. 105, 282–286 (2010).
Muraro, A. et al. Comparison of bullying of food-allergic versus healthy schoolchildren in Italy. J. Allergy Clin. Immunol. 134, 749–751 (2014).
Shemesh, E. et al. Child and parental reports of bullying in a consecutive sample of children with food allergy. Pediatrics 131, e10–e17 (2013).
Annunziato, R. A. et al. Longitudinal evaluation of food allergy-related bullying. J. Allergy Clin. Immunol. Pract. 2, 639–641 (2014).
van der Velde, J. L. et al. Food allergy-related quality of life after double-blind, placebo-controlled food challenges in adults, adolescents, and children. J. Allergy Clin. Immunol. 130, 1136–1143.e2 (2012).
Franxman, T. J., Howe, L., Teich, E. & Greenhawt, M. J. Oral food challenge and food allergy quality of life in caregivers of children with food allergy. J. Allergy Clin. Immunol. Pract. 3, 50–56 (2015).
Epstein Rigbi, N. et al. Patient quality of life following induction of oral immunotherapy for food allergy. Pediatr. Allergy Immunol. 27, 263–268 (2016).
Factor, J. M., Mendelson, L., Lee, J., Nouman, G. & Lester, M. R. Effect of oral immunotherapy to peanut on food-specific quality of life. Ann. Allergy Asthma Immunol. 109, 348–352.e2 (2012).
LeBovidge, J. S. et al. Evaluation of a group intervention for children with food allergy and their parents. Ann. Allergy Asthma Immunol. 101, 160–165 (2008).
Baptist, A. P. et al. A self-regulation intervention can improve quality of life for families with food allergy. J. Allergy Clin. Immunol. 130, 263–265.e6 (2012).
Kelleher, M. M. et al. Twenty four-hour helpline access to expert management advice for food-allergy-triggered anaphylaxis in infants, children and young people. A pragmatic, randomized controlled trial. Allergy 68, 1598–1604 (2013).
Herbert, L., Shemesh, E. & Bender, B. Clinical management of psychosocial concerns related to food allergy. J. Allergy Clin. Immunol. Pract. 4, 205–213 (2016).
Shreffler, W. G., Beyer, K., Chu, T.-H. T., Burks, A. W. & Sampson, H. A. Microarray immunoassay: association of clinical history, in vitro IgE function, and heterogeneity of allergenic peanut epitopes. J. Allergy Clin. Immunol. 113, 776–782 (2004).
Lin, J. et al. A bioinformatics approach to identify patients with symptomatic peanut allergy using peptide microarray immunoassay. J. Allergy Clin. Immunol. 129, 1321–1328.e5 (2012).
Nowak-Wegrzyn, A. et al. Tolerance to extensively heated milk in children with cow's milk allergy. J. Allergy Clin. Immunol. 122, 342–347.e2 (2008).
Lemon-Mule, H. et al. Immunologic changes in children with egg allergy ingesting extensively heated egg. J. Allergy Clin. Immunol. 122, 977–983.e1 (2008).
Hefle, S. L. et al. Consumer attitudes and risks associated with packaged foods having advisory labeling regarding the presence of peanuts. J. Allergy Clin. Immunol. 120, 171–176 (2007).
Flinterman, A. E. et al. Peanut epitopes for IgE and IgG4 in peanut-sensitized children in relation to severity of peanut allergy. J. Allergy Clin. Immunol. 121, 737–743.e10 (2008).
Wanich, N., Nowak-Wegrzyn, A., Sampson, H. A. & Shreffler, W. G. Allergen-specific basophil suppression associated with clinical tolerance in patients with milk allergy. J. Allergy Clin. Immunol. 123, 789–794.e20 (2009).
MacGlashan, D. JR. Expression profiling of human basophils. Modulation by cytokines and secretagogues. PloS ONE 10, e0126435 (2015).
1,000 Days. Good nutrition in the 1,000 days between a woman's pregnancy and her child's second birthday sets the foundation for all the days that follow. 1,000 Days http://thousanddays.org/ (2017).
Schäfer, T. et al. S3-Guideline on allergy prevention. 2014 update: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Society for Pediatric and Adolescent Medicine (DGKJ). Allergo J. Int. 23, 186–199 (2014).
Blander, J. M., Longman, R. S., Iliev, I. D., Sonnenberg, G. F. & Artis, D. Regulation of inflammation by microbiota interactions with the host. Nat. Immunol. 18, 851–860 (2017).
Aagaard, K. et al. The placenta harbors a unique microbiome. Sci. Transl Med. 6, 237ra65 (2014).
Magne, F., Puchi Silva, A., Carvajal, B. & Gotteland, M. The elevated rate of Cesarean section and its contribution to non-communicable chronic diseases in Latin America: the growing involvement of the microbiota. Front. Pediatr. 5, 192 (2017).
Subramanian, S. et al. Cultivating healthy growth and nutrition through the gut microbiota. Cell 161, 36–48 (2015).
Subramanian, S. et al. Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature 510, 417–421 (2014).
Venkataraman, D. et al. Filaggrin loss-of-function mutations are associated with food allergy in childhood and adolescence. J. Allergy Clin. Immunol. 134, 876–882.e4 (2014).
Kusunoki, T. et al. SPINK5 polymorphism is associated with disease severity and food allergy in children with atopic dermatitis. J. Allergy Clin. Immunol. 115, 636–638 (2005).
Galand, C. et al. IL-33 promotes food anaphylaxis in epicutaneously sensitized mice by targeting mast cells. J. Allergy Clin. Immunol. 138, 1356–1366 (2016).
Genuneit, J. et al. Overview of systematic reviews in allergy epidemiology. Allergy 72, 849–856 (2017).
Du Toit, G., Tsakok, T., Lack, S. & Lack, G. Prevention of food allergy. J. Allergy Clin. Immunol. 137, 998–1010 (2016).
Guillet, G. & Guillet, M. H. Natural history of sensitizations in atopic dermatitis. A 3-year follow-up in 250 children. Food allergy and high risk of respiratory symptoms. Arch. Dermatol. 128, 187–192 (1992).
Martin, P. E. et al. Which infants with eczema are at risk of food allergy? Results from a population-based cohort. Clin. Exp. Allergy 45, 255–264 (2015).
Tsakok, T. et al. Does atopic dermatitis cause food allergy? A systematic review. J. Allergy Clin. Immunol. 137, 1071–1078 (2016).
Prescott, S. & Allen, K. J. Food allergy. Riding the second wave of the allergy epidemic. Pediatr. Allergy Immunol. 22, 155–160 (2011).
Panjari, M. et al. Nut allergy prevalence and differences between Asian-born children and Australian-born children of Asian descent. A state-wide survey of children at primary school entry in Victoria, Australia. Clin. Exp. Allergy 46, 602–609 (2016).
Klemans, R. J. B. et al. The diagnostic value of specific IgE to Ara h 2 to predict peanut allergy in children is comparable to a validated and updated diagnostic prediction model. J. Allergy Clin. Immunol. 131, 157–163 (2013).
Masthoff, L. J. N. et al. Sensitization to Cor a 9 and Cor a 14 is highly specific for a hazelnut allergy with objective symptoms in Dutch children and adults. J. Allergy Clin. Immunol. 132, 393–399 (2013).
Boyano Martinez, T. et al. Validity of specific IgE antibodies in children with egg allergy. Clin. Exp. Allergy 31, 1464–1469 (2001).