Digestive Tract Food Allergy
Discussions of food allergy are about immune responses to proteins in food. Since every person has antibodies in their blood to some food proteins, you can argue that everyone has immune responses to food. You could then argue that food proteins routinely find their way into tissues and blood where these immune responses occur. If this is true, everyone must feel this activity at some time, and some people must become ill as this immune activity occurs. The unanswered questions are: how many people become ill, how often and with what consequences?
The gastrointestinal tract (GIT) is central to understanding all food allergy mechanisms. In addition to digestion of food and absorption of nutrients, the gastrointestinal tract acts as a secretory organ, and an immune sensing device responsible for immunization against incoming antigens and tolerance to frequently appearing antigens. The permeability of the GIT determines how much antigenic material gets inside. A new born infant has no food tolerance and an overly permeable GIT. If you feed an infant regular food too soon, they will routinely become ill with food allergy.
Walker-Smith stated that: "Gastrointestinal food allergies may be defined as clinical syndromes which are characterized by the onset of gastrointestinal symptoms following food ingestion where the underlying mechanism is an immunologically mediated reaction within the gastrointestinal tract...There are broadly speaking two categories of clinical syndromes which are related to the speed of onset of symptoms: immediate and delayed. Those syndromes that manifest immediately after food ingestion are easy to diagnose and specific IgE tests and prick tests are frequently positive. Those with a delayed onset of up to several days are difficult to diagnose and currently available investigations may be unsatisfactory for routine use."
Saavedra-Delagado and Metcalfe reviewed mechanisms of food antigens causing gastrointestinal disease. They detailed the pattern of cow's milk induced gastroenteropathy in children, another prototype of food allergic disease, which manifests as chronic diarrhea and is not associated with positive skin tests to cow's milk proteins. They noted associated symptoms included chronic rhinitis and recurrent otitis media. Gluten enteropathy and dermatitis herpetiformis are reviewed - both disorders acting as prototypes of gluten allergy. Walker reviewed the intestinal uptake of food antigens, developing further the idea of type III immune mechanisms involving circulating immune complexes as the basis of systemic forms of food allergy. Protein-losing enteropathy occurs in children and adults, presenting as edema, anemia, and growth failure or weight loss. This syndrome is associated with eosinophilic infiltration in intestinal biopsies, and eosinophilic debris (Charcot-Laden bodies) in the stool. Food allergy will also cause a non-specific malabsorption syndrome associated with chronic diarrhea. Villous atrophy may be patchy in the small intestine and can missed by a single biopsy. Following an infectious gastroenteritis, both viral and bacterial, hypersensitivity reactions to food are common and in infants may present as a postenteritis milk-protein intolerance.
Ciprandi and Canonica reported that 132 of 236 patients with cutaneous manifestations of food allergy had gastrointestinal diseases - 17.8% presenting with irritable bowel, 13.5 % with constipation, and 11% with ulcer-like dyspepsia. MacDonald and Spenser demonstrated that activated T-cells in the human small intestine produce enteropathy. They stated that: "Intestinal damage as a result of allergy and infection is a major cause of morbidity in man and animals. In intestinal allergy the commonly seen lesions are small intestinal villous atrophy and crypt cell hyperplasia resulting in malabsorption due to a decreased intestinal surface and decreased digestive enzyme levels in intestinal cells." They suggested food antigens stimulate lymphocytes to secrete lymphokines and proliferate. Further studies have revealed increase cytokine levels IL-2 and IFN-gamma, secreted by activated lymphocytes.
Surface Sensing & Reacting System
The gastrointestinal tract acts as selective surface of entry to the body. The gut mucosa is a sensing-reacting, nutrient processing surface. The surface lining of the digestive tract is the largest and most critical interface between the organism and its environment. A constant flow of potentially pathogenic microorganisms into the digestive tract is the biggest challenge to body defenses. The strong acid in the stomach kills some organisms. The pH switches abruptly in the jejunum to alkaline and digestive enzymes begin to act on microbial membranes. Vomiting and diarrhea are defensive responses to the ingestion of microbial toxins. All the defenses against infection can be turned on by food antigens, so that “food allergy” in the gut is a prevalent problem.
The lining epithelial cells are involved in immune processes. They transfer immunoglobulins produced by lamina propria B-lymphocytes to the surface and interact with other cells of the immune system to induce an inflammatory response to microbial invasion. The epithelial cells have many functions including the processing of dietary antigens, expression of class I and II MHC antigens, presentation of antigens to lymphocytes, expression of adhesive molecules mediating interaction with intraepithelial lymphocytes and components of extracellular matrix, production of cytokines and probable participation in T cell development of intraepithelial lymphocytes. Both epithelial cells and intraepithelial lymphocytes participate in inflammatory reactions. Epithelial cells proliferate in celiac disease. Crypt hyperplasia is a common tissue response to mucosal damage in food allergy and infection.
Secretory IgA is essential to mucosal surface defenses and deficiency of this antibody impairs antigen-exclusion mechanisms. Patients with IgA deficiency are likely to have increased gut permeability and may show increased evidence of delayed patterns of food allergy and diseases that are related to type 3 and 4 mechanisms, the "autoimmune diseases". An increased incidence of celiac disease, rheumatoid arthritis, SLE, pernicious anemia, pulmonary hemosiderosis has been reported in IgA deficient patients. There is increased incidence of antibodies to food antigens. The diet of patients with IgA deficiency may require adaptive diet revision. If symptoms develop, the therapeutic strategy is to reduce food antigen loading to compensate for increased antigen entry.
The gastrointestinal tract mucosa secretes a variety of peptide mediators in response to food stimulation, and may release prostaglandin, leukotrienes and cytokines that cause systemic symptoms such as flushing, fever, sweating, fatigue, and cognitive dysfunction. The gastrointestinal tract may "leak" and allow the passage of antigenic molecules into the lymphatics or blood. Systemic disease is downstream from a reactive, leaky gastrointestinal tract. The surface epithelium is a sophisticated nutrient processor-transporter, influenced by immune cells that lie below and between epithelial cells.
Gliadin-specific T lymphocytes are found in the small intestinal mucosa and in the peripheral blood. The density of T cells is increased in the jejunal epithelium, an abnormality considered specific for celiac disease. Gluten specific T cell clones activated in situ by gluten play a central part in the pathogenesis of celiac disease. Antigen induced production of cytokines was studied in lymphocytes which secreted interferon (IFN) gamma, often at high concentrations (2000 U/ml); some secreted in addition interleukin (IL) 4, IL 5, IL 6, IL 10, tumor necrosis factor (TNF), and transforming growth factor (TGF) beta. High IFN gamma concentrations in combination with TNF alpha, might be involved in several pathological features of the celiac lesion. In a review of GIT immunology, Castro and Arntzen suggested that: " The regulation of epithelial and smooth muscle functions by the local immune system represents an exquisitely sensitive adaptation to local antigen challenge ...immunologic cells communicate with nerves via paracrine secretions to rapidly transduce antigenic signals into panmucosal changes in function. These local immunocyte-nerve interactions are modulated by the autonomic and central nervous systems."