Page 653 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPTEr 45 Food Allergy 627

FPIES is a non–IgE-mediated disease usually occurring in KEY CONCEPTS
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infants. Characteristic symptoms of FPIES manifest as repetitive
emesis with or without diarrhea accompanied by lethargy occur- Risk Factors for Fatal Food-Induced
ring 2–4 hours after ingestion of the offending food protein. Allergic Reactions
The risk of abrupt volume loss, hypotension, and potential for Peanut and/or tree nut allergy
bowel perforation makes this a medical emergency. Treatment Delay in administration of autoinjectable epinephrine
is reliant on rehydration. Ondansetron may be helpful in managing Preexisting and/or poorly controlled asthma
acute FPIES reactions. Milk and soy are most commonly impli- Concomitant use of beta-blocker medications
cated, along with less common food allergens, such as rice, oats, Teen and young adult age groups
fruits, or vegetables. FPIES is outgrown in the majority of affected
children by 3 years of age but may be protracted for many years of the relevant allergen; (iii) glycosylation residues; (iv) water
in a smaller subset of patients. solubility; and (v) resistance to heat and digestion. These char-
Celiac disease is an immune-based reaction to gluten, a storage acteristics allow the proteins to stay intact until reaching the
protein for wheat, barley, and rye. The small intestine is typically small intestine, where they initiate a T-helper cell-2 (Th2) response
affected in genetically predisposed individuals, and symptoms that results in production of specific IgE and eventual allergic
resolve with gluten avoidance. Symptoms of celiac disease are disease. Glycosylation refers to the reaction by which carbohydrates
variable and may include diarrhea, steatorrhea, weight loss, are attached to molecules: in food allergens, the carbohydrate
bloating, flatulence, abdominal pain, and also non-GI symptoms, is most often attached to a protein. Carbohydrate residues sur-
such as abnormal results on liver function tests, iron deficiency rounding proteins may be important in initiating the immune
anemia, bone disease, and skin disorders. Celiac disease is detected response. For example, interaction with DC-specific intercellular
with serological testing of celiac-specific antibodies and confirmed adhesion molecule–grabbing nonintegrin (DC-SIGN), a c-type
by duodenal mucosal biopsy, both of which should be performed lectin expressed on APCs that identifies conserved carbohydrate
while the patient is on a gluten-containing diet. 11 residues, has been shown to mediate recognition of the major
peanut protein, Ara h 1. This interaction allows DC activation
PATHOPHYSIOLOGY and Th2 skewing of naïve human T cells.
Once the Th2 response is initiated, it is strengthened through
Food allergy results from a breakdown of oral tolerance (or the induction of interleukin-4 (IL-4) signaling. IL-4 signals B
failure to develop it); foods which are ordinarily harmless may cells to undergo class-switch recombination and begin producing
then trigger an immune response that results in harmful adverse IgE. Basophils have been implicated as a likely contributor of
symptoms upon exposure. Maintaining tolerance requires a early IL-4 production and may play an important role in priming
delicate balanced effort from multiple arms of the immune system. the T-cell response to allergens.
Deviation from the protective response may result in the develop-
ment of an allergic response. The Allergic Response
Allergenic food proteins that survive the initial stages of digestion
PROPERTIES OF FOOD ALLERGENS are taken up by the APCs in MALT. Mucosal DCs may encounter
antigen through (i) extending dendrites through the paracellular
An intact GI mucosal barrier is required to maintain tolerance. space between epithelial cells to sample luminal contents; (ii)
The first line of defense against the mucosal immune system is directly interacting with the epithelial cells; and (iii) taking up
a hydrophobic layer of mucin oligosaccharides, which serve to antigen in the Peyer patch. Once contact with the antigen is
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trap antigen. Secretory IgA is also a part of the outer layer of established, the antigen is processed and loaded onto major
intestinal defense against dietary antigens. Dietary antigens must histocompatibility complex (MHC) class II molecules on the
then penetrate the intestinal epithelium, which is maintained cell surface, costimulatory molecules necessary for T-cell activation
by epithelial junction complexes (adherens junctions) and tight are upregulated, and chemotaxis to the draining lymph node
junctions. Intestinal epithelial barrier dysfunction may play a occurs. Once a DC encounters a T-cell receptor with the same
role in food allergen sensitization. Alterations in the integrity of specificity as the peptide antigen, an immune response ensues.
junctional complexes may be induced by calcineurin inhibitors, In the presence of cytokines, such as IL-4, IL-5, and IL-13, the
and this can result in food allergen sensitization. Genetic defects, responding T cell is programmed to be a Th2 cell. The Th2 cell
such as those in individuals with filaggrin mutations, a protein that will then signal B cells to generate IgE antibodies.
binds to keratin and is important for epithelial cell integrity, may Soluble IgE that is produced by B cells circulates and binds to
predispose individuals to increased risk of EoE. Other factors that the surface of mast cells and basophils. Mast cells are found in
have been shown to affect intestinal permeability include viruses, skin, the gut, and the respiratory tract and are located adjacent
alcohol, and nonsteroidal anti-inflammatory drugs (NSAIDs). to nerves and blood vessels. When an allergen is encountered and
These environmental exposures may alter intestinal epithelial recognized by cell-bound IgE, calcium influx ensues, activating
integrity, thus allowing antigen to interact with the next layer of the mast cell. Once activated, the mast cell degranulates and
defense, mucosa associated lymphoid tissue (MALT; Chapter 20). releases vasoactive compounds and proteases, including histamine,
MALT is composed of lymphocytes, antigen-presenting cells platelet-activating factor, tryptase, chymase, carboxypeptidase, and
(APCs), stromal cells, and other immune cells in the lamina heparin, resulting in the characteristic symptoms of an allergic
propria. It is within MALT that dendritic cells (DCs) interact reaction: urticaria, angioedema, flushing, nausea, vomiting,
with dietary antigens. abdominal pain, diarrhea, wheezing, coughing/bronchospasm,
There are several common characteristics among the most rhinorrhea, and hypotension/syncope. Symptoms may occur
commonly allergenic foods: (i) relatively small molecular weight, alone or in combination and typically appear within minutes
generally less than 70 kilodaltons (kDa); (ii) an abundant source of ingestion.