Immune disorders of the gastrointestinal tract

Immune homeostasis in the gut is the result of a delicate balance between peaceful coexistence with commensal microbiota, immunomodulatory effects of dietary antigens, and appropriate responses to pathogens. Immune disorders of the gut arise when defects in the integrity of these components lead to a dysregulated immune response to the commensal environment. Primary immunodeficiency syndromes can present with intestinal inflammation but are commonly characterized by an increased susceptibility to infections in childhood. Secondary immunodeficiency can occur in a protein-losing enteropathy where loss of immunoglobulins and lymphocytes increase susceptibility to infections, or as a result of metabolic diseases (e.g. diabetes or liver cirrhosis), infections (e.g. HIV), or drugs (e.g. chemotherapy). Immunosuppressive medication can not only lead to secondary immunodeficiency but in the context of neutropenia, cytotoxic gastrointestinal mucosal injury can lead to neutropenic typhlitis. Graft-versus-host disease arises from host antigen-presenting cells engaging with donor T cells and triggering an inflammatory cascade. Immunotherapy with checkpoint inhibitors can have significant gastrointestinal immune-related adverse effects, most notably enterocolitis. Autoimmune diseases can impact gastrointestinal function. Autoimmune dysautonomia can result in gastrointestinal-specific dysmotility and systemic IgG4-related disease can lead to autoimmune pancreatitis. Systemic autoimmune diseases can have gastrointestinal manifestations related to the primary autoimmune process or as an adverse effect of treatment. Hypersensitivity reactions to dietary antigens (e.g. peanuts) result in food allergies and can be either IgE or non-IgE mediated. Food intolerance which is not immunologically mediated is the result of pharmacological (e.g. monosodium glutamate), enzyme-related (e.g. lactose intolerance), or noncoeliac gluten sensitivity. Eosinophilic gastrointestinal tract disorders are often associated with a food allergen: treatment is with steroids and avoidance of the allergen.