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Immune disorders of the gastrointestinal tract 

Immune disorders of the gastrointestinal tract

Immune disorders of the gastrointestinal tract

D.J. Unsworth



Autoimmunity and the gastrointestinal tract—description of a rare monogenic autoimmune condition, IPEX 1 (immunodysregulation, polyendocrinopathy, enteropathy).

Coeliac disease—expanded discussion of genetic background and pathogenesis.

Skin prick tests—discussion of use of serum-based assays to determine optimal timing.

Antibody tests—comment on allergen component specific IgE antibody tests, which may have enhanced specificity, and a cautionary note regarding other non-IgE tests that must be interpreted with extreme caution.

Updated on 28 Nov 2012. The previous version of this content can be found here.
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date: 25 March 2017

The gastrointestinal tract is protected by gut-associated lymphoid tissue that provides an environment where interaction occurs between luminal antigen and specially adapted immune tissue in Peyer’s patches (small intestine only) or lymphoid follicles. T and B lymphocytes primed in the gut migrate into the systemic circulation via the thoracic duct but home preferentially to the lamina propria of the intestine. Plasma cells of the lamina propria secrete immunoglobulin A as a dimer linked by a joining peptide.

Ingestion of antigen can lead to local immunity, systemic immunity, or a state of specific immune unresponsiveness (tolerance). Normally, the intestinal immune system steers a course between immunological incompetence on the one hand, with vulnerability to ingested pathogens, as in primary and secondary immunodeficiencies, and hypersensitivity to dietary antigens on the other, with immunologically mediated adverse reactions each time that antigen is eaten.

Immunodeficiency disorders

Common variable immunodeficiency provides an example of the intestinal complications of primary antibody deficiency syndromes, with 30% to 50% of patients having gastrointestinal problems at some time: achlorhydria is common; there is an increased risk of gastric cancer and B cell lymphoma; infestation with Giardia lamblia and infection with cryptosporidium or campylobacter are common causes of diarrhoea and/or malabsorption; nodular lymphoid hyperplasia is frequently asymptomatic.

Secondary immunodeficiency disorders, e.g. AIDS, are far more common than primary immunodeficiencies. The gastrointestinal tract is a major target organ in HIV infection, with intestinal consequences arising from (1) direct infection of enterocytes by HIV; (2) opportunistic and other infections; and (3) opportunistic tumours.

Food allergy and intolerance

Food allergy refers to a form of exaggerated reactivity (hypersensitivity) of the immune system to an ingested antigen, and is mostly synonymous with reactions involving IgE antibodies. The term ‘food intolerance’ should be used to describe all abnormal, reproducible reactions to food when the causative mechanism is unknown or is not immunological. These are controversial topics—public perception is that a wide variety of symptoms are due to food ‘allergy’, but this is rarely supported by objective scientific evidence. It is highly debatable whether food intolerance plays any part in symptoms remote from the gut—e.g. attention-deficit hyperactivity disorder or intractable epilepsy in children, or arthritis in adults—but food allergy and intolerance remain particularly susceptible to those advocating unorthodox diagnostic tests or treatments, the main hazard of which is that potentially serious problems can be misdiagnosed or mistreated.

Most cases of IgE-mediated food allergic reactions occur in infants and children: in many patients the sensitivity is outgrown. In 80% of cases, relatively few foods—cow’s milk (in infants), peanuts, tree nuts, wheat, eggs, soya, fish, and shellfish—account for symptoms. These are typically easy to diagnose because of the clear relationship between immediate (within minutes) symptoms (e.g. angioedema, urticaria, vomiting, diarrhoea) and exposure. Food allergy should not be diagnosed without good clinical indications, and no laboratory test can replace a careful clinical history. Skin prick tests and tests for circulating antigen-specific IgE antibodies are positive in about 75% of patients with IgE-mediated acute reactions to foods. Recognition of the offending food and its elimination from the diet is the cornerstone of treatment. Some patients (especially those with concurrent asthma) require a preloaded syringe of adrenaline (epinephrine) for self-injection, together with clear instruction and training in its use (see Chapter 17.2).

Elimination diets and food challenges form the basis of diagnosis of food intolerance, the gold standard being a double-blind, placebo-controlled challenge under medical supervision (there is danger of precipitating an adverse reaction, particularly in children), although this is difficult to undertake in practice. Laboratory tests are of little diagnostic help for most patients with food intolerance.

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