Gastrointestinal Transport of Macromolecular Food Antigens Presenter: Joseph A. Bellanti, M.D. Professor of Pediatrics and Microbiology-Immunology, Director, International Center for Interdisciplinary Studies of Immunology, Georgetown University Medical Center, Washington, DCThe gastrointestinal tract not only serves a nutritive function but also is a major immunologic organ containing approximately 2/3 of the entire lymphoid system of the body, housing the antigen-presenting cells, T cells and B cells. These cells are found individually dispersed or may be present within organized lymphoid structures within the tissue of the intestine, referred to as the gut-associated lymphoid tissues (GALT). The Peyer's patches are concentrated in the ileum, the lower part of the small intestine, and represent the anatomic site at which most major interactions of cells occur. Recent studies in children with developmental diseases of the central nervous system (CNS), i.e., ADD, ADHD, autism, have demonstrated a pathologic lesion in the mucosal (membrane) tissues of the ileum, ileal lymphoid nodular hyperplasia, ( ILNH), a possible disease producing overgrowth, which appears to be central to the pathogenesis of these disorders. Although the mechanism(s) by which these lesions occur are not known, it has been suggested that a wide variety of triggers may be involved such as food additives, infections (viral, bacterial, yeast-Candida) and vaccines (measles vaccine). ILHN may represent a pivotal focus to the pathogenesis of a wide variety of immunologically-mediated diseases involving the skin, respiratory tract, gastrointestinal tract and the CNS. (Editor's comment: These lesions may be the cause of many disorders.)Immunologically-mediated diseases include atopic dermatitis, allergic rhinitis, asthma, gastrointestinal allergy, ADHD and autism. Although these disorders occur in different distinct organ sites, two recent finds substantiate a common pathogenetic focus linking these disorders to the gastrointestinal tract.Several children with gastrointestinal symptoms, mainly chronic diarrhea, abdominal pain and failure to thrive, neurological and behavioral clinical manifestations, once diagnosed with food allergy and with elimination of offending food, symptoms have subsided with significant clinical improvement. The gastrointestinal (stomach/gut) tract has dual nutritive and defense functions. The most simple and primitive organisms constantly struggle for their existence; they give chase to living organisms in order to obtain food, and they defend themselves against other organisms in order that they may not become their prey. When the aggressor in this struggle is much smaller than its adversary, the result is that the former introduces itself into the body of the latter and destroys it by means of infection. It takes up its abode in its adversary in order to absorb the contents of its host and to produce within it one or more generations. The gut is the largest reservoir of peripheral nerves in the body and is also a major endocrine organ of internal secretion.. The gut contains all the elements of the lymphoid system which are found distributed in the intestinal mucosa at three major sites. Cellular interactions of these various cell types occur with food and microbial antigens from the intestinal lumen. Antigen within the gut lumen is taken up and then presented to micro phage lineage. Following interactions into other cells, they migrate to the general blood circulation. Thus, some cells populate in the intestinal mucosa itself while others migrate to several other cites including the skin, the bronchial mucosa, the salivary glands, the genitourinary tract, various other glands and the gull bladder. It is now recognized that at and following birth and for the first few months of post-natal life, the developing infant does not have a "mucosal barrier" and has a great transport of macromolecular substances across the mucosal barrier. Facilitated by breast feeding, usually around three months of age, the infant acquires this "mucosal barrier", commonly referred to as "gut closure". Breast milk contains many cellular components and growth factors which have been shown to accelerate the maturation of cells of the gastrointestinal immunologic system involved in the degradation processing and elimination of macromolecular substances. Failure or immaturity of this "mucosal barrier" or "gut closure" function may explain the high incidence of food allergy involving the key organ sites of the skin (atopic eczema), respiratory tract (asthma), gastrointestinal tract (colic and diarrhea) and the central nervous system (ADHD). Following ingestion, food undergoes a complicated process of mechanical breakdown, enzymatic digestion within the gastrointestinal tract, detoxification, transport of the end metabolites and assimilation of essential nutrients, amino acids. There are multiple opportunities for malfunction of the system. Normal metabolism would produce no adverse reactions. Hypersensitivity or allergic reaction might represent deficiency of antigen metabolism or antigen handling by cells of the GI immune system. With normal host with normal enzymatic degradation of food with a normal GALT, there would be complete breakdown to and complete utilization of essential nutrients. With deficiencies, there is the strong possibility of absorption of intact or partially degraded food proteins which could serve as "sensitizing components" responsible for the production of food allergy either in a "genetically predisposed" or normal host. The high incidence of food allergy in infants with frequent involvement of skin, respiratory tract or gastrointestinal tract lends support to this hypothesis. Several immunologic and non-immunologic mechanisms can be involved in the development of food allergy and not all food allergy is caused by IgE-mediated reactions. Knowledge and understanding of these pathogenetic mechanisms may provide new insights into the diagnosis, management, treatment and prevention of Macromolecular Transport and Immunologically-Mediated Diseases (IMD) and related CNS disorders such as ADHD.Ileal Lymphoid Nodular Hyperplasia, Non IgE Food Allergy and ADHD Presenter: Aderbal Sabra, M.D., PhD, Immunology Center, Georgetown University Medical Center, Washington, D.C. and the Department of Pediatrics and Gastroenterology, Universidade do Grande Rio School of Medicine, Rio de Janeiro, Brazil Dr. Sabra described and presented tables outlining specific clinical findings together with results of immunologic and gastrointestinal (GI) studies conducted in various groups of children with GI and behavioral manifestations. Biopsies contained moderate to severe inflammatory infiltrate. No neurological abnormalities at MRI but EEG showed abnormality compatible with the diagnosis of ADHD. Clinical and laboratory findings indicate that ileal-lymphoid-nodular hyperplasia (ILNH), found in terminal ileum, seen in children with ADHD, food allergy, and autism, may be the hallmark lesion of the gastrointestinal tract in patients with food allergy and CNS developmental disorders and may represent the tissue response linking these entities. We (Drs. Bellanti and Sabra) hypothesize that the gastrointestinal lesion allows the entry of food antigens across the inflamed mucosa of the bowel as a result of the reactive inflammatory response in the gastrointestinal tract.In closing, he said, "Rather than putting a label on a child, it is more important to ask these questions, 'What is this child lacking that he needs?' and 'What is this child receiving that he doesn't need?'"