Gastrointestinal food allergy: New insights into pathophysiology and clinical perspectives
2005; Elsevier BV; Volume: 128; Issue: 4 Linguagem: Inglês
10.1053/j.gastro.2004.08.015
ISSN1528-0012
AutoresStephan C. Bischoff, Sheila E. Crowe,
Tópico(s)Celiac Disease Research and Management
ResumoAdverse reactions to food that result in gastrointestinal symptoms are common in the general population; while only a minority of such individuals will have symptoms due to immunologic reactions to foods, gastrointestinal food allergies do exist in both children and adults. These immune reactions are mediated by immunoglobulin E-dependent and -independent mechanisms involving mast cells, eosinophils, and other immune cells, but the complexity of the underlying mechanisms of pathogenesis have yet to be fully defined. Knowledge of the spectrum of adverse reactions to foods that affect the digestive system, including gastrointestinal food allergy, is essential to correctly diagnose and manage the subset of patients with immunologically mediated adverse reactions to foods. Potentially fatal reactions to food necessitate careful instruction and monitoring on the part of health care workers involved in the care of individuals at risk of anaphylaxis. New methods of diagnosis and novel strategies for treatment, including immunologic modulation and the development of hypoallergenic foods, are exciting developments in the field of food allergy. Adverse reactions to food that result in gastrointestinal symptoms are common in the general population; while only a minority of such individuals will have symptoms due to immunologic reactions to foods, gastrointestinal food allergies do exist in both children and adults. These immune reactions are mediated by immunoglobulin E-dependent and -independent mechanisms involving mast cells, eosinophils, and other immune cells, but the complexity of the underlying mechanisms of pathogenesis have yet to be fully defined. Knowledge of the spectrum of adverse reactions to foods that affect the digestive system, including gastrointestinal food allergy, is essential to correctly diagnose and manage the subset of patients with immunologically mediated adverse reactions to foods. Potentially fatal reactions to food necessitate careful instruction and monitoring on the part of health care workers involved in the care of individuals at risk of anaphylaxis. New methods of diagnosis and novel strategies for treatment, including immunologic modulation and the development of hypoallergenic foods, are exciting developments in the field of food allergy. Allergic reactions are of concern to both medical care providers and the general population because of a rapidly increasing prevalence during the past few decades.1Kay A.B. Allergy and allergic diseases. First of two parts.N Engl J Med. 2001; 344: 30-37Crossref PubMed Scopus (631) Google Scholar, 2Kay A.B. Allergy and allergic diseases. Second of two parts.N Engl J Med. 2001; 344: 109-113Crossref PubMed Scopus (194) Google Scholar, 3Sampson H.A. Sicherer S.H. Birnbaum A.H. AGA technical review on the evaluation of food allergy in gastrointestinal disorders.Gastroenterology. 2001; 120: 1026-1040Abstract Full Text Full Text PDF PubMed Google Scholar Approximately 20% of the population has been reported to experience adverse reactions to food (ARF) in industrialized nations such as the United States, the United Kingdom, and Germany, with nuts, fruits, and milk among the most common triggers.4Young E. Stoneham M.D. Petruckevitch A. Barton J. Rona R. A population study of food intolerance.Lancet. 1994; 343: 1127-1130Abstract PubMed Scopus (438) Google Scholar, 5Nowak-Wegrzyn A. Conover-Walker M.K. Wood R.A. Food-allergic reactions in schools and preschools.Arch Pediatr Adolesc Med. 2001; 155: 790-795Crossref PubMed Google Scholar, 6Schafer T. Bohler E. Ruhdorfer S. Weigl L. Wessner D. Heinrich J. Filipiak B. Wichmann H.E. Ring J. Epidemiology of food allergy/food intolerance in adults associations with other manifestations of atopy.Allergy. 2001; 56: 1172-1179Crossref PubMed Scopus (134) Google Scholar, 7Kanny G. Moneret-Vautrin D.A. Flabbee J. Beaudouin E. Morisset M. Thevenin F. Population study of food allergy in France.J Allergy Clin Immunol. 2001; 108: 133-140Abstract Full Text PDF PubMed Scopus (279) Google Scholar, 8Sicherer S.H. Munoz-Furlong A. Sampson H.A. Prevalence of peanut and tree nut allergy in the United States determined by means of a random digit dial telephone survey a 5-year follow-up study.J Allergy Clin Immunol. 2003; 112: 1203-1207Abstract Full Text Full Text PDF PubMed Scopus (461) Google Scholar, 9Zuberbier T. Edenharter G. Worm M. Ehlers I. Reimann S. Hantke T. Roehr C.C. Bergmann K.E. Niggemann B. Prevalence of adverse reactions to food in Germany—a population study.Allergy. 2004; 59: 338-345Crossref PubMed Scopus (177) Google Scholar Epidemiologic data indicate that such reactions are caused by different mechanisms, with only about one third of the reactions in children and one tenth of those in adults due to actual food allergy in which there is an abnormal immunologic reaction to food.4Young E. Stoneham M.D. Petruckevitch A. Barton J. Rona R. A population study of food intolerance.Lancet. 1994; 343: 1127-1130Abstract PubMed Scopus (438) Google Scholar, 6Schafer T. Bohler E. Ruhdorfer S. Weigl L. Wessner D. Heinrich J. Filipiak B. Wichmann H.E. Ring J. Epidemiology of food allergy/food intolerance in adults associations with other manifestations of atopy.Allergy. 2001; 56: 1172-1179Crossref PubMed Scopus (134) Google Scholar, 10Sicherer S.H. Food allergy.Lancet. 2002; 360: 701-710Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar, 11Sampson H.A. 9. Food allergy.J Allergy Clin Immunol. 2003; 111: S540-S547Abstract Full Text Full Text PDF PubMed Google Scholar It has been recognized for some time now that perceived food allergy is often not substantiated when evaluated by double-blind placebo-controlled food challenge, the gold standard for diagnosing food allergy. Nonetheless, true food allergies are believed to affect up to 6%–8% of children younger than 10 years of age and 1%–4% of the adult population,4Young E. Stoneham M.D. Petruckevitch A. Barton J. Rona R. A population study of food intolerance.Lancet. 1994; 343: 1127-1130Abstract PubMed Scopus (438) Google Scholar, 5Nowak-Wegrzyn A. Conover-Walker M.K. Wood R.A. Food-allergic reactions in schools and preschools.Arch Pediatr Adolesc Med. 2001; 155: 790-795Crossref PubMed Google Scholar, 6Schafer T. Bohler E. Ruhdorfer S. Weigl L. Wessner D. Heinrich J. Filipiak B. Wichmann H.E. Ring J. Epidemiology of food allergy/food intolerance in adults associations with other manifestations of atopy.Allergy. 2001; 56: 1172-1179Crossref PubMed Scopus (134) Google Scholar, 12Sampson H.A. Update on food allergy.J Allergy Clin Immunol. 2004; 113: 805-819Abstract Full Text Full Text PDF PubMed Scopus (776) Google Scholar a frequency that should result in most medical practitioners seeing cases of food allergy on a regular basis. The majority of ARF are nonimmunologic in origin, with lactose intolerance the most common type worldwide. It is likely that, along with allergic reactions of a more general nature, allergic reactions to food are increasing in prevalence as well; however, except for peanut allergy,13Grundy J. Matthews S. Bateman B. Dean T. Arshad S.H. Rising prevalence of allergy to peanut in children data from 2 sequential cohorts.J Allergy Clin Immunol. 2002; 110: 784-789Abstract Full Text Full Text PDF PubMed Scopus (373) Google Scholar, 14Burks W. Peanut allergy a growing phenomenon.J Clin Invest. 2003; 111: 950-952Crossref PubMed Google Scholar clear data confirming this are lacking. The reasons for the increase of allergic diseases are not entirely apparent as yet, although recent epidemiologic studies suggest that the greater level of hygiene in urbanized populations in industrialized countries might play a central role.15Helm R.M. Burks A.W. Mechanisms of food allergy.Curr Opin Immunol. 2000; 12: 647-653Crossref PubMed Scopus (72) Google Scholar, 16Bjorksten B. The epidemiology of food allergy.Curr Opin Allergy Clin Immunol. 2001; 1: 225-227Crossref PubMed Google Scholar, 17Kalliomaki M. Isolauri E. Role of intestinal flora in the development of allergy.Curr Opin Allergy Clin Immunol. 2003; 3: 15-20Crossref PubMed Scopus (136) Google Scholar The symptoms of allergy range from slight inconveniences to life-threatening shock reactions.18Sampson H.A. Mendelson L. Rosen J.P. Fatal and near-fatal anaphylactic reactions to food in children and adolescents.N Engl J Med. 1992; 327: 380-384Crossref PubMed Google Scholar Food allergy can involve different organ systems such as the oral cavity and digestive tract, the skin, the respiratory tract, and the cardiovascular system. While dermatologic, respiratory, and systemic manifestations of food allergy are well recognized, those reactions manifesting primarily in the digestive tract can be difficult to recognize, diagnose, and treat. This relates to the protean ways food can cause gastrointestinal (GI) symptoms, the relatively poorly understood pathophysiologic mechanisms, and the limited diagnostic methods available to objectively identify afflicted individuals. These deficiencies are, in part, a consequence of the difficulty accessing the GI tract to establish mechanisms of disease and develop methods to diagnose and treat food allergy.19Bischoff S.C. Mayer J.H. Manns M.P. Allergy and the gut.Int Arch Allergy Immunol. 2000; 121: 270-283Crossref PubMed Google Scholar, 20Crowe S.E. Gastrointestinal food allergies do they exist?.Curr Gastroenterol Rep. 2001; 3: 351-357Crossref PubMed Google Scholar Food allergies and other types of ARF manifest primarily with GI symptoms in up to 50% of patients; therefore, many afflicted patients consult specialists in gastroenterology who are, as a group, largely unprepared to meet the challenge of dealing with such cases.21Sicherer S.H. Clinical aspects of gastrointestinal food allergy in childhood.Pediatrics. 2003; 111: 1609-1616PubMed Google Scholar, 22Crespo J.F. Rodriguez J. Food allergy in adulthood.Allergy. 2003; 58: 98-113Crossref PubMed Scopus (65) Google Scholar Often, patients of this nature become classified as being psychosomatic, being functional, or having irritable bowel syndrome without defining the real problem. It has been recognized for some time now that irritable bowel syndrome is often associated with ARF and, in some instances, food allergy might be a mechanism for symptoms in a subgroup of afflicted patients.23Stefanini G.F. Saggioro A. Alvisi V. Angelini G. Capurso L. Di Lorenzo G. Dobrilla G. Dodero M. Galimberti M. Gasbarrini G. Oral cromolyn sodium in comparison with elimination diet in the irritable bowel syndrome, diarrheic type. Multicenter study of 428 patients.Scand J Gastroenterol. 1995; 30: 535-541Crossref PubMed Google Scholar, 24Niec A.M. Frankum B. Talley N.J. Are adverse food reactions linked to irritable bowel syndrome?.Am J Gastroenterol. 1998; 93: 2184-2190Crossref PubMed Scopus (106) Google Scholar, 25Iacono G. Cavataio F. Montalto G. Florena A. Tumminello M. Soresi M. Notarbartolo A. Carroccio A. Intolerance of cow’s milk and chronic constipation in children.N Engl J Med. 1998; 339: 1100-1104Crossref PubMed Scopus (241) Google Scholar, 26Read N.W. Food and hypersensitivity in functional dyspepsia.Gut. 2002; 51: i50-i53Crossref PubMed Google Scholar, 27Spanier J.A. Howden C.W. Jones M.P. A systematic review of alternative therapies in the irritable bowel syndrome.Arch Intern Med. 2003; 163: 265-274Crossref PubMed Scopus (93) Google Scholar The issue of dealing with food allergy becomes even more important now that food allergy has become the most common cause of life-threatening anaphylaxis in industrialized countries.18Sampson H.A. Mendelson L. Rosen J.P. Fatal and near-fatal anaphylactic reactions to food in children and adolescents.N Engl J Med. 1992; 327: 380-384Crossref PubMed Google Scholar, 28Sicherer S.H. Sampson H.A. Bock S.A. Munoz-Furlong A. Underrepresentation of the risk and incidence of anaphylaxis to foods.Arch Intern Med. 2001; 161: 2046-2047Crossref PubMed Google Scholar, 29Bock S.A. Munoz-Furlong A. Sampson H.A. Fatalities due to anaphylactic reactions to foods.J Allergy Clin Immunol. 2001; 107: 191-193Abstract Full Text PDF PubMed Scopus (820) Google Scholar It is clear that confirmed food allergy is treated most successfully by avoidance of food allergens, the mainstay of treatment of food allergy, but supportive medical treatment with epinephrine, antihistamines, and corticosteroids can be beneficial for severe reactions. Despite a substantial understanding of the field, there are unanswered questions. What causes and what prevents food allergy? What are the underlying mechanisms? How does one confirm the diagnosis on an objective basis? Are there alternatives to food antigen avoidance? The focus of this review is on food allergy manifesting in the digestive system and, in particular, the underlying mechanisms. The best characterized abnormal immunologic reaction to food is immediate immunoglobulin (Ig) E-mediated hypersensitivity to food, also termed a type I reaction, involved in the pathogenesis of many cases of asthma, rhinitis, urticaria, and atopic eczema as well as GI ARF. Delayed reactions following immediate IgE-mediated hypersensitivity occur in selected individuals and are characterized by an enhanced cell infiltration of the tissue with inflammatory cells and subsequent tissue damage. These and other cell-mediated immune reactions to food antigens may also operate in the GI tract and are believed to play a role in milk and soy protein enteropathies and in celiac disease.15Helm R.M. Burks A.W. Mechanisms of food allergy.Curr Opin Immunol. 2000; 12: 647-653Crossref PubMed Scopus (72) Google Scholar, 30Brandtzaeg P.E. Current understanding of gastrointestinal immunoregulation and its relation to food allergy.Ann N Y Acad Sci. 2002; 964: 13-45Crossref PubMed Google Scholar, 31Shah U. Walker W.A. Pathophysiology of intestinal food allergy.Adv Pediatr. 2002; 49: 299-316PubMed Google Scholar Immunologic reactions to foods can also involve “mixed IgE- and non-IgE-mediated” and other mechanisms than classic immediate or delayed hypersensitivity. The development of food allergy is dependent on the presence of several risk factors to be discussed (Table 1). This report, which emphasizes new information reported since the topic of GI food allergy was last reviewed in Gastroenterology 13 years ago,32Crowe S.E. Perdue M.H. Gastrointestinal food hypersensitivity basic mechanisms of pathophysiology.Gastroenterology. 1992; 103: 1075-1095PubMed Google Scholar also examines the clinical aspects of food allergy affecting the gut.Table 1Risk Factors for the Development of Food AllergyImmature mucosal immune systemEarly introduction of solid foodHereditary increase in mucosal permeabilityIgA deficiency or delayed IgA productionInadequate challenge of the intestinal immune system with commensal floraGenetically determined bias toward a Th2 environmentPolymorphisms of Th2 cytokine or IgE receptor genesImpaired enteric nervous systemImmune alterations (eg, low levels of TGF-β)Gastrointestinal infections Open table in a new tab The intestinal mucosa is perpetually exposed to potentially harmful nutrients, microbes, and toxins. On the one hand, absorption of nutrients and controlled uptake of antigens is crucial for life and for development of the mucosal immune system; on the other hand, the host must protect itself against pathogens and allergens.33Brandtzaeg P. Development and basic mechanisms of human gut immunity.Nutr Rev. 1998; 56: S5-S18Crossref PubMed Google Scholar Innate immune mechanisms and other nonspecific defense systems are critical to meet this challenge. These include gastric acid, bicarbonate, and mucus secretion, an intact epithelial layer forming tight junctions, digestive enzymes, peristaltic movement, alternative complement pathways, phagocytes, and more recently defined antimicrobial peptides such as defensins and cathelicidins.34Boman H.G. Innate immunity and the normal microflora.Immunol Rev. 2000; 173: 5-16Crossref PubMed Scopus (223) Google Scholar, 35Zasloff M. Antimicrobial peptides in health and disease.N Engl J Med. 2002; 347: 1199-1200Crossref PubMed Scopus (140) Google Scholar, 36Ganz T. Defensins antimicrobial peptides of innate immunity.Nat Rev Immunol. 2003; 3: 710-720Crossref PubMed Scopus (1189) Google Scholar Such mechanisms are involved in the prevention of infection, control of invasion, and replication of pathogens and possibly allergen exposure within the GI tract. For example, increased sensitization to food antigens has been shown in humans and animal models treated with proton pump inhibitors and with other antisecretory drugs, likely due to less effective gastric proteolysis at neutral pH.37Untersmayr E. Scholl I. Swoboda I. Beil W.J. Forster-Waldl E. Walter F. Riemer A. Kraml G. Kinaciyan T. Spitzauer S. Boltz-Nitulescu G. Scheiner O. Jensen-Jarolim E. Antacid medication inhibits digestion of dietary proteins and causes food allergy a fish allergy model in BALB/c mice.J Allergy Clin Immunol. 2003; 112: 616-623Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar Macrophages and neutrophils have been suggested to be the most important effector cells of the innate immune system, but evidence exists that other cells such as mast cells and eosinophils are also involved.38Medzhitov R. Janeway Jr., C. Innate immunity.N Engl J Med. 2000; 343: 338-344Crossref PubMed Scopus (1097) Google Scholar, 39Wedemeyer J. Tsai M. Galli S.J. Roles of mast cells and basophils in innate and acquired immunity.Curr Opin Immunol. 2000; 12: 624-631Crossref PubMed Scopus (213) Google Scholar These cells recognize conserved bacterial structures through “pattern recognition receptors,” including the recently identified Toll-like receptor family.40Wagner H. Toll meets bacterial CpG-DNA.Immunity. 2001; 14: 499-502Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar The function of the innate immune system is supported by the specific immune system. The notion that undigested macromolecules such as food allergens pass through the intestinal barrier as intact proteins, interacting with the local intestinal immune system and being transported to other body sites such as the skin or the lung, was questioned for many years. However, several studies indicate that macromolecules such as ovalbumin are taken up by the intestinal mucosa and can be detected in peripheral blood.41Sanderson I.R. Walker W.A. Uptake and transport of macromolecules by the intestine possible role in clinical disorders (an update).Gastroenterology. 1993; 104: 622-639PubMed Google Scholar, 42Beier R. Gebert A. Kinetics of particle uptake in the domes of Peyer’s patches.Am J Physiol. 1998; 275: G130-G137PubMed Google Scholar This process was named “persorption” and seems to occur at limited rates under normal conditions that might be of importance for the development of tolerance. However, in infants with an intestinal mucosa not fully matured or in adults with an impaired barrier, increased uptake of macromolecules occurs that may have clinical consequences. The amount of absorbed undigested protein is dependent on genetic factors and variables such as dietary intake, maturity of digestive processes, and the presence of structural or functional abnormalities of the GI tract. Intestinal permeability is increased in patients with food allergy, suggesting that the uptake of food antigens is elevated in food-allergic patients.32Crowe S.E. Perdue M.H. Gastrointestinal food hypersensitivity basic mechanisms of pathophysiology.Gastroenterology. 1992; 103: 1075-1095PubMed Google Scholar, 43Troncone R. Caputo N. Florio G. Finelli E. Increased intestinal sugar permeability after challenge in children with cow’s milk allergy or intolerance.Allergy. 1994; 49: 142-146Crossref PubMed Google Scholar This may be secondary, caused at least in part by secondary inflammatory events such as infection, reduced perfusion, malnutrition, and extraintestinal inflammation. Antigen-presenting cells in the intestinal mucosa differ from other antigen-presenting cells regarding their low expression of costimulatory molecules such as CD80 (B7-1) and CD86 (B7-2), interacting with CD28 and other counterreceptors on T cells.44Rugtveit J. Bakka A. Brandtzaeg P. Differential distribution of B7.1 (CD80) and B7.2 (CD86) costimulatory molecules on mucosal macrophage subsets in human inflammatory bowel disease (IBD).Clin Exp Immunol. 1997; 110: 104-113Crossref PubMed Google Scholar This contributes to the usual hyporesponsive state of the GI immune system, because antigen presentation through major histocompatibility complex class II proteins without further costimulatory signals preferentially induces T-cell anergy or deletion. In contrast, the up-regulation of costimulatory molecules, which is a characteristic feature of uncontrolled inflammation, could drive an inappropriate immune response.44Rugtveit J. Bakka A. Brandtzaeg P. Differential distribution of B7.1 (CD80) and B7.2 (CD86) costimulatory molecules on mucosal macrophage subsets in human inflammatory bowel disease (IBD).Clin Exp Immunol. 1997; 110: 104-113Crossref PubMed Google Scholar, 45Rogler G. Hausmann M. Spottl T. Vogl D. Aschenbrenner E. Andus T. Falk W. Scholmerich J. Gross V. T-cell co-stimulatory molecules are upregulated on intestinal macrophages from inflammatory bowel disease mucosa.Eur J Gastroenterol Hepatol. 1999; 11: 1105-1111Crossref PubMed Google Scholar The immune response is regulated by the form of costimulation (CD80/CD28 interactions favor a T-helper cell [Th] 1-type response, CD86/CD28 interactions favor a Th2-type response), the type of dendritic cells (plasmacytoid/lymphoid dendritic cells generate Th2-type responses, myeloid dendritic cells generate Th1-type responses), and the cytoplasmic milieu (eg, prostaglandin E2 induces the development of plasmacytoid dendritic cells, interferon [IFN]-γ induces interleukin [IL]-12-producing myeloid dendritic cells).46Kuchroo V.K. Das M.P. Brown J.A. Ranger A.M. Zamvil S.S. Sobel R.A. Weiner H.L. Nabavi N. Glimcher L.H. B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways application to autoimmune disease therapy.Cell. 1995; 80: 707-718Abstract Full Text PDF PubMed Google Scholar, 47Steinbrink K. Wolfl M. Jonuleit H. Knop J. Enk A.H. Induction of tolerance by IL-10-treated dendritic cells.J Immunol. 1997; 159: 4772-4780PubMed Google Scholar, 48Kapsenberg M.L. Hilkens C.M. Wierenga E.A. Kalinski P. The paradigm of type 1 and type 2 antigen-presenting cells. Implications for atopic allergy.Clin Exp Allergy. 1999; 29: 33-36Crossref PubMed Google Scholar, 49Bellou A. Schaub B. Ting L. Finn P.W. Toll receptors modulate allergic responses interaction with dendritic cells, T cells and mast cells.Curr Opin Allergy Clin Immunol. 2003; 3: 487-494Crossref PubMed Scopus (19) Google Scholar, 50Zamoyska R. Lovatt M. Signalling in T-lymphocyte development integration of signalling pathways is the key.Curr Opin Immunol. 2004; 16: 191-196Crossref PubMed Scopus (25) Google Scholar The Th1/Th2 balance is further regulated by more recently characterized T-cell subtypes down-regulating both types of immune responses by secreting transforming growth factor (TGF)-β (Th3 cells) and IL-10 (Tr1 cells). TGF-β and IL-10 are relevant cytokines promoting the isotype switch cells from IgM to IgA production in B cells and antigen-specific anergy in T cells, respectively.51Chong S.U. Worm M. Zuberbier T. Role of adverse reactions to food in urticaria and exercise-induced anaphylaxis.Int Arch Allergy Immunol. 2002; 129: 19-26Crossref PubMed Scopus (22) Google Scholar, 52Groux H. O’Garra A. Bigler M. Rouleau M. Antonenko S. De Vries J.E. Roncarolo M.G. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis.Nature. 1997; 389: 737-742Crossref PubMed Scopus (2564) Google Scholar, 53Groux H. Bigler M. De Vries J.E. Roncarolo M.G. Interleukin-10 induces a long term antigen-specific state in human CD4+ T cells.J Exp Med. 1996; 184: 19-29Crossref PubMed Scopus (569) Google Scholar Gut homeostasis is achieved not only by the regulation of barrier function but also by down-regulating the normal immune response to bacteria and food antigens. This phenomenon was termed “oral tolerance” because it is induced following oral challenge with particular antigens. This phenomenon, primarily described in the rodent system, also exists in humans and confers not only a local but also a systemic tolerance against orally administered antigen.54Weiner H.L. Friedman A. Miller A. Khoury S.J. Al-Sabbagh A. Santos L. Sayegh M. Nussenblatt R.B. Trentham D.E. Hafler D.A. Oral tolerance immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens.Ann Rev Immunol. 1994; 12: 809-837Crossref PubMed Google Scholar, 55Gutgemann I. Fahrer A.M. Altman J.D. Davis M.M. Chien Y.H. Induction of rapid T cell activation and tolerance by systemic presentation of an orally administered antigen.Immunity. 1998; 8: 667-673Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar, 56Nagler-Anderson C. Tolerance and immunity in the intestinal immune system.Crit Rev Immunol. 2000; 20: 103-120Crossref PubMed Google Scholar Active down-regulatory mechanisms comprise different nonspecific (gastric acid, mucus, epithelial barrier) and specific immunologic systems (secretory IgA [sIgA]- and secretory IgM-producing plasma cells, tolerogenic antigen-presenting cells and immunosuppressive T cells, T-cell anergy and apoptosis). Such mechanisms, which have been described in detail elsewhere, are crucial to developing tolerance to dietary antigens.53Groux H. Bigler M. De Vries J.E. Roncarolo M.G. Interleukin-10 induces a long term antigen-specific state in human CD4+ T cells.J Exp Med. 1996; 184: 19-29Crossref PubMed Scopus (569) Google Scholar, 57Chen Y. Inobe J. Marks R. Gonnella P. Kuchroo V.K. Weiner H.L. Peripheral deletion of antigen-reactive T cells in oral tolerance.Nature. 1995; 376: 177-180Crossref PubMed Google Scholar The typical hyporesponsiveness of the intestinal immune system seems to be impaired in intestinal inflammatory diseases such as inflammatory bowel disease and also food allergy.11Sampson H.A. 9. Food allergy.J Allergy Clin Immunol. 2003; 111: S540-S547Abstract Full Text Full Text PDF PubMed Google Scholar, 30Brandtzaeg P.E. Current understanding of gastrointestinal immunoregulation and its relation to food allergy.Ann N Y Acad Sci. 2002; 964: 13-45Crossref PubMed Google Scholar, 58Duchmann R. Kaiser I. Hermann E. Mayet W. Ewe K. Meyer zum Buschenfelde K.H. Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD).Clin Exp Immunol. 1995; 102: 445-447PubMed Google Scholar Moreover, the immaturity or breakdown of such mechanisms may increase the risk of sensitization to dietary proteins and subsequently of developing food allergy. Adequate challenge of the intestinal immune system with commensal microorganisms and other stimuli is required for full maturation of the adaptive immune system and, in particular, the sIgA defense system. It has been suggested that reduced stimulatory reinforcement of the developing mucosal immune system in individuals residing in states of enhanced cleanliness might contribute to the increased frequency of allergy and autoimmune disorders in industrialized countries.16Bjorksten B. The epidemiology of food allergy.Curr Opin Allergy Clin Immunol. 2001; 1: 225-227Crossref PubMed Google Scholar, 59Warner J.O. The hygiene hypothesis.Pediatr Allergy Immunol. 2003; 14: 145-146Crossref PubMed Scopus (14) Google Scholar, 60Kalliomaki M. Salminen S. Poussa T. Arvilommi H. Isolauri E. Probiotics and prevention of atopic disease 4-year follow-up of a randomised placebo-controlled trial.Lancet. 2003; 361: 1869-1871Abstract Full Text Full Text PDF PubMed Scopus (735) Google Scholar This “hygiene hypothesis” is supported by the findings that probiotics such as lactobacilli and bifidobacteria strains can enhance sIgA responses in a T-cell-dependent manner and that nonenteropathogenic Escherichia coli or Lactobacillus GG reduce infection and protect against the development of food-induced atopic dermatitis.60Kalliomaki M. Salminen S. Poussa T. Arvilommi H. Isolauri E. Probiotics and prevention of atopic disease 4-year follow-up of a randomised placebo-controlled trial.Lancet. 2003; 361: 1869-1871Abstract Full Text Full Text PDF PubMed Scopus (735) Google Scholar, 61Lodinova-Zadnikova R. Cukrowska B. Tlaskalova-Hogenova H. Oral administration of probiotic Escherichia coli after birth reduces frequency of allergies and repeated infections later in life (after 10 and 20 years).Int Arch Allergy Immunol. 2003; 131: 209-211Crossref PubMed Scopus (97) Google Scholar In this respect, it is interesting to note that breast-feeding may protect against infection and atopy, likely because of the delivery of sIgA and other protective molecules such as TGF-β and IL-10 through breast milk.62Saarinen U.M. Kajosaari M. Breastfeeding as prophylaxis against atopic disease prospective follow-up study until 17 years old.Lancet. 1995; 346: 1065-1069Abstract Full Text PDF PubMed Google Scholar, 63Saarinen K.M. Vaarala O. Klemetti P. Savilahti E. Transforming growth factor-beta1 in mothers’ colostrum and immune responses to cows’ milk proteins in infants with cows’ milk allergy.J Allergy Clin Immunol. 1999; 104: 1093-1098Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar, 64Kull I. Wickman M. Lilja G. Nordvall S.L. Pershagen G. Breast feeding and allergic diseases in infants-a prospective birth cohort study.Arch Dis Child. 2002; 87: 478-481Crossref PubMed Scopus (136) Google Scholar Allergic inflammation of the g
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