Food Allergies: The Basics
2015; Elsevier BV; Volume: 148; Issue: 6 Linguagem: Inglês
10.1053/j.gastro.2015.02.006
ISSN1528-0012
AutoresRudolf Valenta, Heidrun Hochwallner, Birgit Linhart, Sandra Pahr,
Tópico(s)Contact Dermatitis and Allergies
ResumoIgE-associated food allergy affects approximately 3% of the population and has severe effects on the daily life of patients—manifestations occur not only in the gastrointestinal tract but also affect other organ systems. Birth cohort studies have shown that allergic sensitization to food allergens develops early in childhood. Mechanisms of pathogenesis include cross-linking of mast cell– and basophil-bound IgE and immediate release of inflammatory mediators, as well as late-phase and chronic allergic inflammation, resulting from T-cell, basophil, and eosinophil activation. Researchers have begun to characterize the molecular features of food allergens and have developed chip-based assays for multiple allergens. These have provided information about cross-reactivity among different sources of food allergens, identified disease-causing food allergens, and helped us to estimate the severity and types of allergic reactions in patients. Importantly, learning about the structure of disease-causing food allergens has allowed researchers to engineer synthetic and recombinant vaccines. IgE-associated food allergy affects approximately 3% of the population and has severe effects on the daily life of patients—manifestations occur not only in the gastrointestinal tract but also affect other organ systems. Birth cohort studies have shown that allergic sensitization to food allergens develops early in childhood. Mechanisms of pathogenesis include cross-linking of mast cell– and basophil-bound IgE and immediate release of inflammatory mediators, as well as late-phase and chronic allergic inflammation, resulting from T-cell, basophil, and eosinophil activation. Researchers have begun to characterize the molecular features of food allergens and have developed chip-based assays for multiple allergens. These have provided information about cross-reactivity among different sources of food allergens, identified disease-causing food allergens, and helped us to estimate the severity and types of allergic reactions in patients. Importantly, learning about the structure of disease-causing food allergens has allowed researchers to engineer synthetic and recombinant vaccines. Heidrun HochwallnerView Large Image Figure ViewerDownload Hi-res image Download (PPT)Birgit LinhartView Large Image Figure ViewerDownload Hi-res image Download (PPT)Sandra PahrView Large Image Figure ViewerDownload Hi-res image Download (PPT) There are several mechanisms by which people develop adverse reactions to foods also termed food intolerance.1Metcalfe D.D. Sampson H.A. Simon R.A. Food allergy: adverse reactions to foods and food additives.3rd ed. Blackwell Science, Malden, MA2003Google Scholar These reactions can be considered toxic or nontoxic (Figure 1).2Bischoff S.C. Sellge G. Immune mechanisms in food-induced disease.in: 3rd ed. Food allergy: adverse reactions to foods and food additives. Blackwell Science, Malden, MA2003: 14-37Google Scholar Among the nontoxic reactions, those that are not immune-mediated, such as those involving enzyme defects (eg, vasoactive amines) or reactions to certain substances (eg lactose intolerance), are far more common than immune-mediated reactions.2Bischoff S.C. Sellge G. Immune mechanisms in food-induced disease.in: 3rd ed. Food allergy: adverse reactions to foods and food additives. Blackwell Science, Malden, MA2003: 14-37Google Scholar Nevertheless, immune-mediated reactions affect millions of people, are responsible for significant morbidity and health care costs, and can cause severe life-threatening reactions that lead to death.3Sicherer S.H. Sampson H.A. Food allergy: epidemiology, pathogenesis, diagnosis, and treatment.J Allergy Clin Immunol. 2014; 133: 291-307Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar, 4Longo G. Berti I. Burks A.W. et al.IgE-mediated food allergy in children.Lancet. 2013; 382: 1656-1664Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar, 5De Silva D. Geromi M. Panesar S.S. et al.Acute and long-term management of food allergy: systematic review.Allergy. 2014; 69: 159-167Crossref PubMed Scopus (17) Google Scholar Food allergy was defined by an expert panel of the National Institute of Allergy and Infectious Diseases as "an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food." This response comprises basically all types of immune-mediated reactions, including those caused by the adaptive and innate immune system (Figure 1).6Boyce J.A. Assa'ad A. Burks A.W. et al.Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-Sponsored Expert Panel Report.J Allergy Clin Immunol. 2010; 126: 1105-1118Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar The term allergy was coined in 1906 by the Austrian pediatrician Clemens von Pirquet,7Von Pirquet C. Allergie.Mnch Med Wochenschrift. 1906; 30: 1457-1458Google Scholar who described cases of serum sickness in children treated with antibody preparations. According to Coombs and Gell,8Coombs R.R.A. Gell P.G.H. Classification of allergic reactions responsible for clinical hypersensitivity and disease.in: 3rd ed. Clin aspects immunol. Blackwell Scientific Publications, Oxford1975: 761-781Google Scholar there are 4 major types of allergic reactions based on pathogenesis mechanisms. The most common forms of immune-mediated adverse reactions to foods (type I reactions) always are characterized by the development of IgE against food allergens. It can be accompanied by inflammation, induced by cellular components, and mediated by T cells and eosinophils. Patients with IgE-associated food allergy can be identified based on the detection of food allergen–specific IgE in serum and body fluids, and by measuring IgE-mediated cellular and in vivo responses.4Longo G. Berti I. Burks A.W. et al.IgE-mediated food allergy in children.Lancet. 2013; 382: 1656-1664Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar Although it is tempting to speculate that food antigen–specific IgG can cause adverse reactions via type II or type III hypersensitivity, there is no solid experimental evidence to support the relevance of these reactions to food allergies that develop in patients (Figure 1). Accordingly, several position papers strongly recommend against testing for food antigen–specific IgG in the diagnosis of food allergy.9Stapel S.O. Asero R. Ballmer-Weber B.K. et al.Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report.Allergy. 2008; 63: 793-796Crossref PubMed Scopus (134) Google Scholar, 10Bock S.A. AAAAI support of the EAACI position paper on IgG4.J Allergy Clin Immunol. 2010; 125: 1410Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar Type IV hypersensitivity, which mainly involves food antigen–specific T-cell responses and can damage the gut mucosa, is associated with disorders such as celiac disease. Celiac disease is characterized by a hypersensitivity reaction against the wheat gluten fraction comprising alcohol soluble gliadins and acid-, alkali-soluble glutenins, accompanied by an autoimmune component.11Schuppan D. Junker Y. Barisani D. Celiac disease: from pathogenesis to novel therapies.Gastroenterology. 2009; 137: 1912-1933Abstract Full Text Full Text PDF PubMed Scopus (264) Google Scholar Type IV hypersensitivity reactions also might be involved in food protein–induced enterocolitis (Figure 1).12Caubet J.C. Ford L.S. Sickles L. et al.Clinical features and resolution of food protein-induced enterocolitis syndrome: 10-year experience.J Allergy Clin Immunol. 2014; 134: 382-389Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar Studies have shown that certain food proteins can induce inflammation via direct activation of the innate immune system. For example, wheat amylase trypsin inhibitors and certain milk oligosaccharides can cause intestinal inflammation via activation of Toll-like receptor 4,13Junker Y. Zeissig S. Kim S.J. et al.Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4.J Exp Med. 2012; 209: 2395-2408Crossref PubMed Scopus (123) Google Scholar, 14Kurakevich E. Hennet T. Hausmann M. et al.Milk oligosaccharide sialyl(α2,3)lactose activates intestinal CD11c+ cells through TLR4.Proc Natl Acad Sci U S A. 2013; 110: 17444-17449Crossref PubMed Scopus (17) Google Scholar and certain allergens have been shown to stimulate the innate immune system.15Ruiter B. Shreffler W.G. Innate immunostimulatory properties of allergens and their relevance to food allergy.Semin Immunopathol. 2012; 34: 617-632Crossref PubMed Scopus (17) Google Scholar Innate immune mechanisms might mediate nonceliac gluten sensitivity.16Catassi C. Bai J.C. Bonaz B. et al.Non-celiac gluten sensitivity: the new frontier of gluten related disorders.Nutrients. 2013; 5: 3839-3853Crossref PubMed Scopus (0) Google Scholar In developed countries, IgE-associated food allergy affects 3%–8% of children and 1%–3% of adults.3Sicherer S.H. Sampson H.A. Food allergy: epidemiology, pathogenesis, diagnosis, and treatment.J Allergy Clin Immunol. 2014; 133: 291-307Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar, 4Longo G. Berti I. Burks A.W. et al.IgE-mediated food allergy in children.Lancet. 2013; 382: 1656-1664Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar, 5De Silva D. Geromi M. Panesar S.S. et al.Acute and long-term management of food allergy: systematic review.Allergy. 2014; 69: 159-167Crossref PubMed Scopus (17) Google Scholar It not only is common, but often is a serious and life-threatening health condition that requires accurate diagnosis and has strong effects on an individual's dietary habits and social life. Milk, eggs, wheat, peanuts, nuts, sesame, fish, fruits, and vegetables are common inducers of IgE-associated food allergy.4Longo G. Berti I. Burks A.W. et al.IgE-mediated food allergy in children.Lancet. 2013; 382: 1656-1664Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar Allergies to foods such as milk, egg, and wheat often are outgrown (patients acquire tolerance), whereas allergies to peanuts, tree nuts, and fish allergies often persists over a lifetime.3Sicherer S.H. Sampson H.A. Food allergy: epidemiology, pathogenesis, diagnosis, and treatment.J Allergy Clin Immunol. 2014; 133: 291-307Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar The exact incidence of food allergies has not been fully established because there are discrepancies among findings from studies in which food allergies were self-reported vs those diagnosed by various assays (eg, provocation, skin test, or serologic tests).4Longo G. Berti I. Burks A.W. et al.IgE-mediated food allergy in children.Lancet. 2013; 382: 1656-1664Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar, 17Burney P.G. Potts J. Kummeling I. et al.The prevalence and distribution of food sensitization in European adults.Allergy. 2014; 69: 365-371Crossref PubMed Scopus (19) Google Scholar The prevalence and severity of food allergies seem to be increasing. In addition to genetic factors, a number of environmental, cultural, and behavioral factors affect the frequency, severity, and type of allergic manifestations in patients.18Lack G. Update on risk factors for food allergy.J Allergy Clin Immunol. 2012; 129: 1187-1197Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar, 19Gray C.L. Levin M.E. Zar H.J. et al.Food allergy in South African children with atopic dermatitis.Pediatr Allergy Immunol. 2014; 25: 572-579PubMed Google Scholar, 20Baumann S. Lorentz A. Obesity-a promoter of allergy?.Int Arch Allergy Immunol. 2013; 162: 205-213Crossref PubMed Scopus (10) Google Scholar, 21Marrs T. Bruce K.D. Logan K. et al.Is there an association between microbial exposure and food allergy? A systematic review.Pediatr Allergy Immunol. 2013; 24: 311-320Crossref PubMed Scopus (19) Google Scholar A recent study identified epigenetic differences in CD4+ T cells from children with IgE-mediated food allergies, compared with children without food allergies—differences such as these might contribute to the development of a food allergy.22Martino D. Joo J.E. Sexton-Oates A. et al.Epigenome-wide association study reveals longitudinally stable DNA methylation differences in CD4+ T cells from children with IgE-mediated food allergy.Epigenetics. 2014; 9: 998-1006Crossref PubMed Scopus (23) Google Scholar According to the hygiene hypothesis, decreases in family size and improvements in personal hygiene have contributed to the increased prevalence of IgE-mediated allergies. On the other hand, factors such as an anthroposophic lifestyle (eating organic foods that contain lactobacilli and restrictive use of antibiotics, antipyretics, and vaccines) have been associated with a reduced incidence of allergies.23Strachan D.P. Hay fever, hygiene, and household size.BMJ. 1989; 299: 1259-1260Crossref PubMed Google Scholar, 24Alm J.S. Swartz J. Björkstén B. et al.An anthroposophic lifestyle and intestinal microflora in infancy.Pediatr Allergy Immunol. 2002; 13: 402-411Crossref PubMed Scopus (60) Google Scholar It has been proposed that insufficient exposure to dietary and bacterial metabolites might have contributed to increases in inflammatory disorders in Western countries.25Thorburn A.N. Macia L. Mackay C.R. Diet, metabolites, and "Western-lifestyle" inflammatory diseases.Immunity. 2014; 40: 833-842Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar The term allergic sensitization describes the first induction of an allergic immune response upon allergen encounter.26Valenta R. The future of antigen-specific immunotherapy of allergy.Nat Rev Immunol. 2002; 2: 446-453Crossref PubMed Google Scholar, 27Valenta R. Ball T. Focke M. et al.Immunotherapy of allergic disease.Adv Immunol. 2004; 82: 105-153Crossref PubMed Scopus (66) Google Scholar Two routes of allergic sensitization are well established (Figure 2A). Class 1 food allergens (eg, milk, egg, or peanut) are oral allergens that cause sensitization via the gastrointestinal tract.28Han Y. Kim J. Ahn K. Food allergy.Korean J Pediatr. 2012; 55: 153-158Crossref PubMed Scopus (8) Google Scholar Class 2 food allergens are aeroallergens (eg, major birch pollen allergen Bet v 1) that cause sensitization via the respiratory tract. Immune responses against these allergens can cross-react with homologous food allergens (eg, major apple allergen Mal d 1) to cause symptoms.29Ortolani C. Ispano M. Pastorello E. et al.The oral allergy syndrome.Ann Allergy. 1988; 61: 47-52PubMed Google Scholar, 30Ebner C. Birkner T. Valenta R. et al.Common epitopes of birch pollen and apples-studies by Western and Northern blot.J Allergy Clin Immunol. 1991; 88: 588-594Abstract Full Text PDF PubMed Scopus (214) Google Scholar, 31Valenta R. Kraft D. Type 1 allergic reactions to plant-derived food: a consequence of primary sensitization to pollen allergens.J Allergy Clin Immunol. 1996; 97: 893-895Abstract Full Text PDF PubMed Scopus (125) Google Scholar It recently was proposed that people become sensitized to food allergens via skin contact, but there have been few studies of this process.18Lack G. Update on risk factors for food allergy.J Allergy Clin Immunol. 2012; 129: 1187-1197Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar Interestingly, studies of animal models have indicated that epicutaneous sensitization leads to expansion of IgE-dependent intestinal mast cells and food-induced allergic reactions.32Bartnikas L.M. Gurish M.F. Burton O.T. et al.Epicutaneous sensitization results in IgE-dependent intestinal mast cell expansion and food-induced anaphylaxis.J Allergy Clin Immunol. 2013; 131: 451-460Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar, 33Noti M. Kim B.S. Siracusa M.C. et al.Exposure to food allergens through inflamed skin promotes intestinal food allergy through the thymic stromal lymphopoietin-basophil axis.J Allergy Clin Immunol. 2014; 133: 1390-1399Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar For an overview of food allergen sources that may cause sensitization via the respiratory tract and skin, see the article by Asero and Antonicelli.34Asero R. Antonicelli L. Does sensitization to foods in adults occur always in the gut?.Int Arch Allergy Immunol. 2011; 154: 6-14Crossref PubMed Scopus (11) Google Scholar Determinants of allergic sensitization include features of the epithelial barrier, the allergen itself (whether allergens are stable and not degraded in the environment or gastrointestinal tract), nonallergenic components of the food matrix, and substances that act as adjuvants (Figure 2A).35Breiteneder H. Mills E.N. Molecular properties of food allergens.J Allergy Clin Immunol. 2005; 115: 14-23Abstract Full Text Full Text PDF PubMed Scopus (185) Google Scholar For example, food allergens have been proposed to have greater stability during digestion than other molecules in food.36Astwood J.D. Leach J.N. Fuchs R.L. Stability of food allergens to digestion in vitro.Nat Biotechnol. 1996; 14: 1269-1273Crossref PubMed Google Scholar Intrinsic factors (eg, genetic factors such as mutations in the filaggrin gene) and exogenous factors (eg, alcohol, anti-inflammatory drugs, pathogens, or stress) have been proposed to reduce the barrier function of the intestinal epithelium and facilitate sensitization.37Groschwitz K.R. Hogan S.P. Intestinal barrier function: molecular regulation and disease pathogenesis.J Allergy Clin Immunol. 2009; 124: 3-20Abstract Full Text Full Text PDF PubMed Scopus (265) Google Scholar, 38Irvine A.D. McLean W.H. Leung D.Y. Filaggrin mutations associated with skin and allergic diseases.N Engl J Med. 2011; 365: 1315-1327Crossref PubMed Scopus (294) Google Scholar, 39Perrier C. Corthésy B. Gut permeability and food allergies.Clin Exp Allergy. 2011; 41: 20-28Crossref PubMed Scopus (52) Google Scholar On the other hand, secretory antibodies, particularly secretory IgA (SIgA), have important roles in reinforcing the epithelial barrier. Mice deficient in SIgA and secretory IgM are prone to develop food allergen–induced anaphylactic shock, which can be overcome by induction of tolerance with T-regulatory cells.40Johansen F.E. Pekna M. Norderhaug I.N. et al.Absence of epithelial immunoglobulin A transport, with increased mucosal leakiness, in polymeric immunoglobulin receptor/secretory component-deficient mice.J Exp Med. 1999; 190: 915-922Crossref PubMed Scopus (237) Google Scholar, 41Karlsson M.R. Johansen F.E. Kahu H. et al.Hypersensitivity and oral tolerance in the absence of a secretory immune system.Allergy. 2010; 65: 561-570Crossref PubMed Scopus (32) Google Scholar Many environmental and genetic factors contribute to the atopic predisposition of individuals. These determine their susceptibility to develop allergic immune responses against allergens.42Grammatikos A.P. The genetic and environmental basis of atopic diseases.Ann Med. 2008; 40: 482-495Crossref PubMed Scopus (34) Google Scholar In atopic individuals who have a predisposition toward developing IgE-associated allergies, encounters with allergen activate, after processing by antigen-presenting cells (eg, dendritic cells or B cells), allergen-specific T-helper 2 (Th2) cells, which produce cytokines such as interleukin (IL)4 and IL13. These cytokines induce class switching and production of allergen-specific IgE.43Paul W.E. Interleukin 4/B cell stimulatory factor 1: one lymphokine, many functions.FASEB J. 1987; 1: 456-461PubMed Google Scholar, 44Romagnani S. The Th1/Th2 paradigm.Immunol Today. 1997; 18: 263-266Abstract Full Text PDF PubMed Google Scholar, 45Vercelli D. Geha R.S. Regulation of isotype switching.Curr Opin Immunol. 1992; 4: 794-797Crossref PubMed Scopus (49) Google Scholar Primary allergic sensitization (such as a class switch toward IgE production) occurs early in life and leads to T-cell and IgE memory, which can be boosted with repeated allergen contact (secondary immune response).46Henderson L.L. Larson J.B. Gleich G.J. Maximal rise in IgE antibody following ragweed pollination season.J Allergy Clin Immunol. 1975; 55: 10-15Abstract Full Text PDF PubMed Scopus (48) Google Scholar, 47Naclerio R.M. Adkinson Jr., N.F. Moylan B. et al.Nasal provocation with allergen induces a secondary serum IgE antibody response.J Allergy Clin Immunol. 1997; 100: 505-510Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar, 48Niederberger V. Ring J. Rakoski J. et al.Antigens drive memory IgE responses in human allergy via the nasal mucosa.Int Arch Allergy Immunol. 2007; 142: 133-144Crossref PubMed Scopus (42) Google Scholar, 49Mojtabavi N. Dekan G. Stingl G. et al.Long-lived Th2 memory in experimental allergic asthma.J Immunol. 2002; 169: 4788-4796Crossref PubMed Google Scholar Upon contact with a primary food allergen, nonallergic individuals produce allergen-specific IgG and IgA, which do not induce allergic reactions. The formation of food allergen–specific IgE is a main feature of IgE-associated food allergy and its diagnosis. Analyses of the time courses of allergic sensitization to respiratory and food allergen sources in large birth cohort studies have shown that food allergies and their associated symptoms develop before respiratory allergies.50Kulig M. Bergmann R. Klettke U. et al.Natural course of sensitization to food and inhalant allergens during the first 6 years of life.J Allergy Clin Immunol. 1999; 103: 1173-1179Abstract Full Text Full Text PDF PubMed Scopus (290) Google Scholar In later life, there is a reverse trend—food allergies often are outgrown and respiratory allergies increase and dominate.50Kulig M. Bergmann R. Klettke U. et al.Natural course of sensitization to food and inhalant allergens during the first 6 years of life.J Allergy Clin Immunol. 1999; 103: 1173-1179Abstract Full Text Full Text PDF PubMed Scopus (290) Google Scholar Interestingly, the prevalence of food allergies is approximately 10-fold lower than that of respiratory allergies.4Longo G. Berti I. Burks A.W. et al.IgE-mediated food allergy in children.Lancet. 2013; 382: 1656-1664Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar, 51Katelaris C.H. Lee B.W. Potter P.C. et al.Prevalence and diversity of allergic rhinitis in regions of the world beyond Europe and North America.Clin Exp Allergy. 2012; 42: 186-207Crossref PubMed Scopus (45) Google Scholar This could be because oral exposure to allergens activates tolerance mechanisms (via regulatory T cells) and less frequently results in allergic sensitization than respiratory exposure to allergens.52Strobel S. Mowat A.M. Oral tolerance and allergic responses to food proteins.Curr Opin Allergy Clin Immunol. 2006; 6: 207-213Crossref PubMed Scopus (82) Google Scholar, 53Chehade M. Mayer L. Oral tolerance and its relation to food hypersensitivities.J Allergy Clin Immunol. 2005; 115: 3-12Abstract Full Text Full Text PDF PubMed Scopus (259) Google Scholar Several cellular mechanisms seem to influence primary allergic sensitization vs tolerance in the intestine. Tolerance can be mediated by antigen presentation by dendritic cells, which interact with C-type lectin receptors54Zhou Y. Kawasaki H. Hsu S.C. et al.Oral tolerance to food-induced systemic anaphylaxis mediated by the C-type lectin SIGNR1.Nat Med. 2010; 16: 1128-1133Crossref PubMed Scopus (79) Google Scholar; dendritic cell–bound IgE can down-regulate allergic inflammation at mucosal sites.55Platzer B. Baker K. Vera M.P. et al.Dendritic cell-bound IgE functions to restrain allergic inflammation at mucosal sites.Mucosal Immunol. 2014; (Epub ahead of print)http://dx.doi.org/10.1038/mi.2014.85Google Scholar Children with an egg allergy were reported to have reduced function of neonatal T-regulatory cells compared with children without an egg allergy.56Smith M. Tourigny M.R. Noakes P. et al.Children with egg allergy have evidence of reduced neonatal CD4(+)CD25(+)CD127(lo/-) regulatory T cell function.J Allergy Clin Immunol. 2008; 121: 1460-1466Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar On the other hand, children who outgrew a cow's milk allergy had increased T-regulatory cell responses.57Karlsson M.R. Rugtveit J. Brandtzaeg P. Allergen-responsive CD4+CD25+ regulatory T cells in children who have outgrown cow's milk allergy.J Exp Med. 2004; 199: 1679-1688Crossref PubMed Scopus (308) Google Scholar These findings indicate that T-regulatory cells modulate the development of food allergies.58Brandtzaeg P. Food allergy: separating the science from the mythology.Nat Rev Gastroenterol Hepatol. 2010; 7: 380-400Crossref PubMed Scopus (72) Google Scholar After primary sensitization, the allergic immune response is boosted with repeated exposure to allergen, increasing activation of allergen-specific T cells and production of IgE. In persons with a respiratory allergy, the IgE response is boosted by contact with a mucosal allergen48Niederberger V. Ring J. Rakoski J. et al.Antigens drive memory IgE responses in human allergy via the nasal mucosa.Int Arch Allergy Immunol. 2007; 142: 133-144Crossref PubMed Scopus (42) Google Scholar and, interestingly, does not seem to require T-cell help.59Egger C. Horak F. Vrtala S. et al.Nasal application of rBet v 1 or non-IgE-reactive T-cell epitope-containing rBet v 1 fragments has different effects on systemic allergen-specific antibody responses.J Allergy Clin Immunol. 2010; 126: 1312-1315Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar, 60Linhart B. Bigenzahn S. Hartl A. et al.Costimulation blockade inhibits allergic sensitization but does not affect established allergy in a murine model of grass pollen allergy.J Immunol. 2007; 178: 3924-3931Crossref PubMed Google Scholar, 61Marth K. Wollmann E. Gallerano D. et al.Persistence of IgE-associated allergy and allergen-specific IgE despite CD4+ T cell loss in AIDS.PLoS One. 2014; 9: e97893Crossref PubMed Scopus (1) Google Scholar Another interesting feature of the established secondary IgE response is that in adults with an allergy, the profile of allergens recognized by IgE does not change substantially, whereas it seems that young children can be sensitized to new allergens.62Lupinek C. Marth K. Niederberger V. et al.Analysis of serum IgE reactivity profiles with microarrayed allergens indicates absence of de novo IgE sensitizations in adults.J Allergy Clin Immunol. 2012; 130: 1418-1420Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar, 63Hatzler L. Panetta V. Lau S. et al.Molecular spreading and predictive value of preclinical IgE response to Phleum pratense in children with hay fever.J Allergy Clin Immunol. 2012; 130: 894-901Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar In the case of a respiratory allergy, allergen contact through the respiratory mucosa strongly boosts IgE production, but has little influence on the other classes of allergen-specific antibodies (eg, IgA or IgG).48Niederberger V. Ring J. Rakoski J. et al.Antigens drive memory IgE responses in human allergy via the nasal mucosa.Int Arch Allergy Immunol. 2007; 142: 133-144Crossref PubMed Scopus (42) Google Scholar The responding B ε memory cells may reside in the respiratory mucosa or the adjacent lymphoid tissues,64Durham S.R. Gould H.J. Thienes C.P. et al.Expression of epsilon germ-line gene transcripts and mRNA for the epsilon heavy chain of IgE in nasal B cells and the effects of topical corticosteroid.Eur J Immunol. 1997; 27: 2899-2906Crossref PubMed Scopus (123) Google Scholar but little is known about the precise location of the cells involved in secondary IgE responses in allergic patients.65Eckl-Dorna J. Pree I. Reisinger J. et al.The majority of allergen-specific IgE in the blood of allergic patients does not originate from blood-derived B cells or plasma cells.Clin Exp Allergy. 2012; 42: 1347-1355Crossref PubMed Scopus (11) Google Scholar The mechanisms by which food allergen–specific IgE responses are boosted in patients with food allergies are poorly understood. When food allergens were administered orally, patients had strong increases in the production of allergen-specific IgG, accompanied by an initial boost of IgE.66Burks A.W. Jones S.M. Wood R.A. et al.Oral immunotherapy for treatment of egg allergy in children.N Engl J Med. 2012; 367: 233-243Crossref PubMed Scopus (191) Google Scholar, 67Nozawa A. Okamoto Y. Movérare R. et al.Monitoring Ara h 1, 2 and 3-sIgE and sIgG4 antibodies in peanut allergic children receiving oral rush immunotherapy.Pediatr Allergy Immunol. 2014; 25: 323-328Crossref PubMed Google Scholar, 68Sato S. Yanagida N. Ogura K. et al.Clinical studies in oral allergen-specific immunotherapy: differences among allergens.Int Arch Allergy Immunol. 2014; 164: 1-9Crossref PubMed Scopus (14) Google Scholar These findings indicated that allergen ingestion can boost allergen-specific production of IgG as well as IgE. It is possible that oral allergens can boost production of disease-causing IgE, as well as that of potentially protective IgG; this might explain why elimination or continued intake of food allergens can benefit patients.69Prescott S.L. Bouygue G.R. Videky D. et al.Avoidance or exposure to foods in preventio
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