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INTRODUCTION
Food allergy is recognized as a common worldwide problem, and, like other atopic disorders, its incidence seems to increase. In the past years, investigations of allergic food proteins and related immunological responses have moved to the molecular level, and the newly-found knowledge might provide novel experimental strategies for the laboratory diagnosis and the immuno-modulatory control of food-induced allergic reactions (1, 2).
Approximately 20% of the population alters their diet for a perceived adverse reaction to food, but the application of double-blind placebo-controlled oral food challenge, the gold standard for diagnosis of food allergy, shows that questionnaire-based studies overestimate the prevalence of food allergies. The clinical disorders determined by adverse reactions to food can be classified on the basis of immunologic or no immunologic mechanisms and the organ system or systems affected (3, 4, 5).
The true prevalence of food allergy is lower and seems to range from 1% to 4% of the general population and about 6% of the general population and about 6% of the paediatric population, but does occur in as much as 25% of children with eczema6. Allergic hypersensitivity simply put, is an adverse immune reaction to a protein (or allergen) in our environment, which is normally harmless to the non-allergic person. It may present as mild itching of the skin, tissue swelling and wheezing or even progress to full-blown anaphylaxis and death. 18 million allergy sufferers live in the UK where 4% of the populations also have a food allergy.
Allergy develops after repeated exposure to the causative allergen. Sensitization takes place on initial exposure (a process that may take up to six weeks to develop) and no adverse reaction appears to occur during initial sensitization (6).
(A) DEFINITION
A food allergy is an immunologic response to a food protein and caused by allergens in the food that are a kind of protein in the food. These proteins resist the cooking process, the acid in the stomach and the enzymes in the stomach and intestines and enter the blood stream and they cause the allergy reaction after they enter the blood stream.
(B) SIGNS AND SYMPTOMS
Symptoms of food allergies are: -
1. Anaphylaxis: a severe, whole-body allergic reaction that can result in death. Leads to vasodilation and, if severe, symptoms of life-threatening shock.
2. Angioedema: rapid swelling (edema) of the skin, mucosa and submucosal tissues, especially of the eyelids, face, lips, and tongue.
3. Eczema is a form of dermatitis, or inflammation of the upper layers of the skin.
(a). Atopic eczema (aka infantile e., flexural e., atopic dermatitis) is believed to have a hereditary component, and often runs in families whose members also have hay fever and asthma. Itchy rash is particularly noticeable on face and scalp, neck, inside of elbows, behind knees, and buttocks.
(b). Contact dermatitis is of two types: allergic (resulting from a delayed reaction to some allergen, such as poison ivy or nickel), and irritant (resulting from direct reaction to a solvent, for example). Some substances act both as allergen and irritant (e.g. wet cement). Other substances cause a problem after sunlight exposure, bringing on phototoxic dermatitis.
(c). Xerotic eczema (aka asteatotic e., e. craquele or craquelatum, winter itch, pruritus hiemalis) is dry skin that becomes so serious it turns into eczema. It worsens in dry winter weather, and limbs and trunk are most often affected. The itchy, tender skin resembles a dry, cracked, river bed. This disorder is very common among the older population.
(d). Seborrhoeic dermatitis (aka cradle cap in infants, dandruff) causes dry or greasy scaling of the scalp and eyebrows. Scaly pimples and red patches sometimes appear in various adjacent places. In newborns it causes a thick, yellow crusty scalp rash called cradle cap which seems related to lack of biotin, and is often curable.
4. Skin rashes, such as nettle rash (also called urticaria or hives). Some of these longer lasting rashes are called atopic dermatitis.
5. Itching of the mouth, throat, eyes, skin, or any area
6. Nausea, vomiting, diarrhoea, stomach cramps, or abdominal pain
7. Running nose or nasal congestion
8. Wheezing, scratchy throat, shortness of breath, or difficulty swallowing
9. Mood swings, depression: The symptoms of an Immunoglobulin E (IgE) allergic reaction can take place within a few minutes to an hour. The process of eating and digesting food affects the timing and location of a reaction. IgG reactions build over a period of hours to days, and therefore symptoms can be difficult to notice as allergy-related (7).
TYPES OF ALLERGENIC FOOD
There are a number of groups of foods that are responsible for causing the majority of food allergies (6). Rice allergy is more common in East Asia where rice forms a large part of the diet. In Central Europe, celery allergy is more common. The top allergens vary somewhat from country to country but milk, eggs, peanuts, tree nuts, fish, shellfish, soy, wheat and sesame tend to be in the top ten in many countries (8).
The most common food allergies are:
1. Milk allergy:-
Two out of a hundred infants under one year old suffer from cows milk allergy, making it the most common food allergy of childhood. In general children lose this sensitivity as they grow up with nine out of ten losing it by the age of three; it is unusual for adults to suffer from this allergy. Symptoms are frequently vomiting and diarrhoea in children, with 30-50% also having skin rashes of some type. A small number of children have an anaphylactic reaction to milk which tends to be life-long.
The major allergens in milk are the caseins and the protein b-lactoglobulin. People are usually allergic to more than one kind of milk protein. The proteins from cows milk are very similar to those from goats and sheep. Thus goats or sheeps milk cannot be used as a cows milk substitute in allergic individuals (8).
A report about 22-year-old Female patient is described who was repeatedly hospitalised on account of severe asthmatic attacks presumably due to the ingestion of cows milk or milk-containing products. There were no signs of gastrointestinal disturbance, but some urticaria and angioedema occurred. Strongly positive RASTs (radioallergosorbent test) were observed in the blood serum against the proteins in cows milk, bovine serum, egg white, cod fish, and house dust. The symptoms were successfully controlled by rigorous dietary measures (8).
2. Eggs:-
Allergy to eggs is usually observed in young children rather than adults, and like cows milk allergy, fades with time. Occasionally children suffer from a severe form of allergy which is not outgrown.
The main allergens are the egg white proteins ovomucoid, ovalbumin, and ovotransferrin. The eggs of other poultry, such as ducks, are very similar to those of hens and can cause reactions in egg-allergic individuals (8).
3. Peanut allergy:-
Peanuts are one of most allergenic foods and frequently cause very severe reactions, including anaphylaxis. Allergy to peanuts is established in childhood and usually maintained throughout life. Peanut allergy can be so severe that only very tiny amounts of peanut can cause a reaction. Thus the traces of nuts found in processed oils, or the carryover of materials on utensils used for serving foods, can be enough in some individuals, to cause a reaction. The main allergens in peanuts and Soya are the proteins used by the seed as a food store for it to grow into a seedling. One of the allergens in Soya bean is very similar to a major allergen from dust mites, a common environmental allergen. We arent sure yet whether this means there is a link between dust allergy and Soya allergy.
A large number of children who develop peanut allergy have their first reaction the first time they are given a peanut-containing product (usually a dab of peanut butter). A large number of children who develop peanut allergy have their first reaction the first time they are given a peanut-containing product (usually a dab of peanut butter). Peanut protein could pass into breast milk Twenty-three lactating women; aged 21 to 35 years ate 50 grams of dry roasted peanuts (about 60 peanuts or 1/3 cup). Breast milk samples were collected at hourly intervals. Peanut protein was found in the breast milk of 11 of the mothers. In 10 mothers, it was detected within two hours after she ate peanuts, in one mother it was detected six hours later.
That peanut protein is secreted into breast milk, thus sensitizing the baby who is at risk for developing an allergy. This may explain why up to 85 percent of children have a peanut allergy reaction the first time they eat a peanut-containing product. A baby born into a family with allergies.
[Note: - Milk, eggs, and wheat have previously been shown to pass into breast milk. The mothers from allergic families eliminate peanuts and tree nuts (e.g., almonds, walnuts, etc.) and consider eliminating eggs, milk, fish, and perhaps other foods from their diets while nursing. If you choose to do this, be sure to speak with a registered dietitian to be sure your diet is well-balanced (8).
4. Tree Nut Allergy:-
This group includes true tree nuts, such as Brazil nuts, hazelnuts, walnut and pecan. Whilst not as intensively studied as peanuts, indications are that tree nuts can cause symptoms as severe which can occasionally be fatal. Children who become sensitised to tree nuts tend to remain allergic throughout life. Hazelnut and almond allergies are more like those people get to fruit, and are linked to pollen allergies. Nut allergens can be both destroyed by, and resistant, to cooking and we think that roasting may actually create new allergens. The allergens can be the seed storage proteins, or other molecules which are also found in pollen.
5. Fish and shellfish allergy:-
Allergies to shellfish are unusual in children, mostly being experienced by adults. Reactions to fish are found in children and adults. The incidence of seafood allergy is higher in those countries with a high consumption of fish and shellfish. Severe reactions are more frequently found with these foods, including anaphylaxis. Cooking does not destroy the allergens in fish and shellfish, and some individuals maybe allergic to the cooked, but not raw, fish. The major allergens in fish are flesh proteins called parvalbumins which are very similar in all kinds of fish. Shellfish allergens are usually found in the flesh and are part of the muscle protein system, whilst in foods such as shrimps, allergens have also been found in the shells.
If pregnant or trying to be, avoid seafood and shellfish. Some believe that it may cause your child to develop food allergy.
6. Fruits allergy:-
In general allergic reactions to fruits and vegetables are mild, and are often limited to the mouth, and are called the oral-allergy syndrome (OAS). Around four out of ten people having OAS are also allergic to tree and weed pollens. Thus people who are allergic to birch pollen are much more likely to be allergic to apples. There allergens in fruits and vegetables are not as complicated as other foods. Many of them are very like the allergens in pollens, which is why people with pollen allergies are also allergic to certain fruits.
Many fruit allergens are destroyed by cooking, and thus cooked fruits are often safe for fruit allergic people to eat. Allergies to latex gloves, especially amongst health professionals, are increasing. As many of the latex allergens are like those found in certain tropical fruits, such as bananas, these people can get an allergic reaction to handling or eating these foods (8). Tomato Allergy: - Reported on four cases (two adults with throat constriction, one child with gastro esophageal reflux disease [GERD], one child with atopic dermatitis) with IgE-mediated reactions to tomatoes.
Using extracts prepared from the skin, seeds, and fleshy fruit of the tomato, specific IgE antibody in the sera of patients was detected by ELISA. After characterizing the extracts for their antigen profile and reactivity with IgE, proteins were separated by SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis). Of the four patients, one adult showed higher IgE against tomato skin extract. Western blot tests of the patients scrum with tomato skin extract also revealed reaction with a protein band in the 42-45kD region. Tomato allergy can be manifested as atopic dermatitis, laryngeal angioedema, and even gastroesophageal reflux.
7. Cereals allergy:
Suffered by children and adults alike, wheat allergy appears to be particularly associated with exercise-induced anaphylaxis. The more of a cereal (wheat, rye, barley, oats, maize or rice) we eat the more likely we are to suffer an allergy. Thus rice allergy is found more frequently in populations eating ethnic diets. Seed storage proteins (such as wheat gluten) and other proteins present in grain to protect it from attack by moulds and bacteria, have been found to be major allergens.
8. Penicillins allergy reaction:
Frequently manifestations are – rash, itching, urticaria and fever. Wheezing, angioneuritis, edema, serum sickness and exofolliative dermatitis are less common. Anaphylaxis is rare but may be fatal. Fear of anaphylactic shock has several restricted the use of injPnG in general practice. All form of penicillin (natural or semi synthetic) can cause allergy but it is more commonly seen after parenteral administration.
Penicillin produce hypersensitivity – urticaria, angioedema, bronchiospasm, anaphylaxis or serum sickness. If earlier reaction had been only a rash, penicillin may be given cautiously – often no untoward effect is seen. History of penicillin allergy must be elicited before injection it. A scratch test on intradermal test (with 2 – 10 u ) may be performed first. On occasion, his it has caused fatal anaphylaxis. Testing with benzyl-penicilloyl – polylysine is safer. However a negative intradermal test does not rule out delayed hypersensitivity. It should also be released that presence of antibodies to penicillin does not mean allergy to it, because practically everyone who receives penicillin develop antibodies to it.
For the development of antibodies, penicillin or a product of it (mostly penicilloyl moiety – major determent) act as a hapten. Topical use of penicillin is highly sensitizing (contact dermatitis and other reaction). Therefore, all topical preparation of penicillin (including eye ointment) have been banned, except for use in eye as solution in case of gonococcal opthalmia (9).
CLASSIFICATION OF FOOD ALLERGY
1. IMMEDIATE REACTION TYPE (SKIN-SENSITIVE OR WHEAL TYPE)
Antibody: Skin sensitizing:-
A. Hereditary: spontaneous, abrupt, obvious, often severe symptoms, Involving all major systems of body Portal of entry:
(a) Alimentary mucosa causes: food by ingestion
(b) Respiratory mucosa causes: Inhaled dusty airborne food dusts and volatile food odours by inhalation (rare)
(c) Skin causes: food by percutaneous absorption (rare)
(d) By parenteral injection causes: Therapeutic agent containing food excitants
B. Nonhereditary: Induced, anaphylactic, often severe symptoms involving all major system of body
Portal of entry: By parenteral injection causes: sensitizers such as organ extracts, virus vaccines (egg media)
2. DELAYED REACTION TYPES (SKIN-NEGATIVE OR NON- WHEALTYPE)
Antibody: unknown:-
A. Hereditary: Deliberate, obscure symptoms involving all major systems
Of body
Portal of entry: Alimentary mucosa causes: Foods by ingestion
B. Nonhereditary: Induced (contact dermatitis), rare, involving respiratory and cutaneous systems
Portal of entry: Intact oral, and buccal mucosa, and skin causes: Foods, essential oils of foods and spices (10).
PATHOPHYSIOLOGY
A food allergy is an immunologic response to a food protein Food allergy is type 1 hypersensitivity reaction. Type I Hypersensitivity is characterised by excessive activation of mast cells and basophils by IgE, resulting in a systemic inflammatory response that can result in symptoms as benign as a runny nose, to life-threatening anaphylactic shock and death.
Exposure to an allergen activates B cells to form IgE secreting plasma cells . The secreted IgE Molecules bind to IgE specific Fc Receptor on mast cells. Second Exposure to allergen leads to cross linking of the bound IgE triggering release of pharmacologically active mediators vasoactive amines (11).
Immunoglobulin E (IgE):
The potent biological activity of IgE allowed it to be identified in serum despite its extremely low average serum concentration (0.3microgram/ml).IgE antibodies mediate the immediate hypersensitivity reaction that are responsible for the symptoms of hay fever, asthma, hives and anaphylactic shock. When the appropriate antigen was later injected at the same site, a wheal and flare reaction developed there .this reaction, called the p-k reaction was the basis for the first biological assay for IgE activity.
IgE binds to Fc receptors on the membranes of blood basophils and tissue mast cells, Cross-linkage or receptor bound IgE molecules by antigen (allergen) induces basophils and mast cells to translocation their granules to the plasma membrane and release their contents to the extracellular environment, a process known as degranulation. As a result, a variety of pharmacologically active mediators are released and given rise to allergic manifestations.
Fc Receptors:
Many cells feature membrane glycoproteins called Fc receptors (FcR) that have an affinity for the Fc portion of the antibody molecule. These receptors are essential for many of the bioligocal functions of antibodies. An FcR binds IgE like: The cytoplasmic domains of the chains of FcRI are associated with protein tyrosine kinase (PTKs). Crosslinkage of the FcRI receptors activates the associated PTKs, resulting in the phosphorylation of tyrosines within the ITAMs of the subunit as well as phosphorylation of residue on the subunit and on phospholipace C. These phosphyrylation events incduce the producton of a number of second messengers that mediate the process of degranulation.
Within 15 s after crosslinkage of FcRI, methylation of various membrane phospholipids is observed, resulting in an increase in membrane fluidity and the formation of Ca2+ channels. An increase of Ca2+ reaches a peak within 2 min. of FcRI crosslinkage. This increase is due both to the uptake of extracellular Ca2+ and to a release of Ca2+ from nitracellular stores in the endoplasmic reticulum. The Ca2+ increase eventually leads to the formation of arachidonic acid, which is converted into two classes of potent mediators: prostaglandins and leukotrienes. The increase of Ca2+ also promotes the assembly of microtubules and the contraction of microfilaments, both of which are necessary for the movement of granules to the plasma membrane. The importance of the Ca2+ increase in mast-cell degranulation is highlighted by the use of drugs, such as disodium cromoglycate (cromolyn sodium), that block this influx as a treatment for allergies (11).
Concomitant with phospholipid methylation and Ca2+ increase, there is a transient increase in the activity of membrane-bound adenylate cyclase, with a rapid peak of its reaction product, cyclic adenosine monophosphate (cAMP), reached about one min. after crosslinkage of FcRI. The effect of cAMP is exerted through the activation of cAMP-dependent protein kinases, which phosphorylate proteins on the granule membrane, thereby changing the permeability of the granules to water and Ca2+. The consequent swelling of the granules facilitates their fusion with the plasma membrane, releasing their contents. The increase in cAMP is transient and is followed by a drop in cAMP to levels below baseline. This drop in cAMP appears to be necessary for degranulation to proceed; when cAMP levels are increased by certain drugs, the degranulation process is blocked. Histamines are the main mediator of food allergy (11).
IgE Crosslinkage Initiates Degranulation
The biochemical events the mediate degranulaton of mast cells and blood basophils have many features in common. For simplicity, this section presents a general overview of mast-cell degranulation mechanisms without calling attention to the slight differences between mast cells and basophils. Although mast-cell degranulation generally is initiated by allergen crosslinkage of bound IgE, a number of other stimuli can also initiate the process, including the anaphylatoxins (C3a, C4a, and C5a) and various drugs. This section focuses on the biochemical events that follow allergen crosslinkage of bound IgE as follows
Receptor Crosslinkage
IgE-mediated degranulation begins when an allergen cross links IgE that is bound (fixed) to the Fc receptor on the surface of a mast cell or basophil. In itself, the binding of IgE to FcRI apparently has no effect on a target cell. It is only after allergen crosslinks the fixed IgE-receptor complex that degranulation proceeds. The importance of crosslinkage is indicated by the inability of monovalent allergens, which cannot crosslink the fixed IgE, to trigger degranulation.
Genetic basis
There is much evidence to support the genetic basis of allergy, as allergic parents are more likely to have allergic children, and their allergies are likely to be stronger than those from non-allergic parents. However some allergies are not consistent along genealogies with parents being allergic to peanuts, but having children allergic to ragweed, or siblings not sharing the same allergens. Ethnicity has also been shown to play a role in some allergies. Interestingly, in regard to asthma, it has been suggested that different genetic loci are responsible for asthma in people of Caucasian, Hispanic, Asian, and African origins. It has also been suggested that there are both general atopy genes and tissue-specific allergy genes that target the allergic response to specific mucosal tissues. Potential disease associated alleles include both coding region variation and SNPs. Caucasian people seem to have the most asthma (11).
DIAGNOSIS OF FOOD ALLERGY
Diagnosis of food allergy is based on clinical history, skin prick tests, and laboratory tests to detect serum-food specific IgE, elimination diets and challenges (12).
1. History: The physician interviews the patient to determine if the facts are consistent with a food allergy. . The doctor asks such questions as: What was the timing of the reaction? Did the reaction come on quickly, usually within an hour after eating the food? Was treatment for allergy successful? For example, if hives stem from a food allergy, antihistamines should relieve them. Is the reaction always associated with a certain food? Did anyone else get sick? For example, if the person has eaten fish contaminated with histamine, everyone who ate the fish should be sick. In an allergic reaction, however, only the person allergic to the fish becomes ill.
2. Dietary Diary: To keep a record of the contents of each meal and whether reactions occurred that are consistent with allergy. The dietary diary provides more details than the oral history, so that the doctor and patient can better determine if there is a consistent relationship between a food and the allergic reactions.
3. Elimination Diet: The next step is an elimination diet. The patient does not eat a food suspected of causing the allergy, for example, eggs, and substitutes another food, in this instance, another source of protein. If after the patient removes the food, the symptoms go away, the doctor almost always can make a diagnosis of food allergy. This technique is also not suitable if the allergic reactions have been infrequent13.
4. Skin Prick Tests: The skin prick is easy to do and results are available in minutes. Different allergists may use different devices for skin prick testing. Some use a bifurcated needle , which looks like a fork with two prongs. Others use a multi-test , which may look like a small board with several pins sticking out of it (14).
In a scratch-the-skin test, a dilute extract of the suspected food is placed on the skin of the forearm or back. This portion of the skin then is scratched with a needle and observed for swelling or redness, which would signify a local allergic reaction to the food. A positive scratch test indicates that the patient has the IgE that is specific for the food being tested on the skins mast cells. In some highly allergic patients, however, especially if they have had anaphylactic reactions, skin tests should not be done because they could provoke another dangerous reaction. Skin tests also cannot be done in patients with extensive eczema (13).
It is good for quickly learning if a person is allergic to a particular food or not, because it detects allergic antibodies known as IgE. Skin tests cannot predict if a reaction would occur or what kind of reaction might occur if a person ingests that particular allergen. They can however confirm an allergy in light of a patients history of reactions to a particular food. This almost painless procedure allows the tested protein to interact with food-specific IgE on the surface of skin mast cells (12).
A device, such as a lancet, plastic probe or tip of a small gauge needle, is pressed through a commercial extract of food and a positive (histamine) and negative (saline-glycerine) controls into the epidermis. Allergens eliciting within 15 min a wheal at least 3 mm larger than that produced by the negative control are considered positive, indicating the possibility that the patients have symptomatic reactivity to the specific food, with strongly positive results implying a greater likelihood of clinical reactivity. When evaluating allergy to fruits and vegetables, commercially prepared extracts are often inadequate because they are prone to degradation, and therefore the fresh food might be used for prick-by-prick test. A number of investigators have examined the use of the atopy patch test in addition to skin prick test for the diagnosis of non-IgE-mediated food allergy, with delayed reactions to food, but at this time, there are no standardized reagents or methods of application and interpretation. Thus, its diagnostic accuracy remains still controversial, especially in older children (12).
In Eosinophilic gastroenteritis associated with food allergy and bronchial asthma. A skin prick test and RAST (radioallergosorbent test) to causative food allergens showed a negative result. A fiber-optic endoscopic biopsy from the gastric mucosa showed an intense eosinophilic infiltration. The fiber-optic endoscopic biopsy might be needed to identify coexisting EG if an allergic patient with blood eosinophilia complains of severe gastrointestinal symptoms (14).
5. Blood Tests:- Blood tests such as the RAST (radioallergosorbent test) and the ELISA (enzyme-linked immunosorbent assay). These tests measure the presence of food-specific IgE antibodies in the blood of patients, but they cost more than skin tests, and the results are not available immediately (13).
In RAST, blood is drawn and sent to a lab for testing to determine predictive values for certain foods. These predictive values can be compared to the RAST blood test results. If a persons RAST score is higher than the predictive value for that food, then there is over a 95% chance the person will have an allergic reaction (limited to rash and anaphylaxis reactions) if they ingest that food. Currently, predictive values are available for the following foods: milk, egg, peanut, fish, soy, and wheat. Blood tests allow for hundreds of allergens to be screened from a single sample, and cover food allergies as well as inhalants. However, non-IgE mediated allergies cannot be detected by this method. Blood testing methodologies currently available that can measure antibodies of IgG are not acceptable as a method of allergy evaluation. IgG-type anitbodies are not implicated in food allergy reactions15.
(A) In vitro IgE food allergen-specific assays:-
The in vitro IgE assay is less sensitive, however, then the epicutaneous skin test. The in vitro IgE assay uses the same commercial food extract16.
1. Redioallergosorbeny (RAST):- The first test using this new technology was the redioallergosorbent test (RAST). The first step requires coupling the allergen (e.g., cows milk protein) to solid support (e.g., a paper disk). When this disk is placed in a test tube with patient serum, the coupling of antibodies directed against milk or that were anti- cows milk in nature (this includes IgE, M, A, or E class) occurs. After washing, the third step is the addition of radio-labelled (I125) rabbit antihuman IgE antibodies .these antibodies will attach themselves only to the IgE antimilk antibodies( which in turn are coupled to the cows milk protein in the paper disk). Then the amount of radioactivity can be measured, and thus the amount of cows milk-allergen-anti-IgE cows milk antibody can be quantities (16).
2. Enzyme-Linked Immunosorbent Assay (ELISA) :- This is more recent type of test, but is just like the RAST test except for two factors. First, allergen is usually coupled to the inner surface of small plastic walls (into which the patients serum and other ingredients of the test are placed). The second, and more important, difference is the final quantitative factor. In the ELISA system, an enzyme coupled to the antihuman IgE denatures a substrate, which either change color or becomes fluorescent. Then the amount of color or fluorescence can be measured(16).
(B) The production of interferon-gamma in response to a major peanut allergy, Ara h II correlates with serum levels of IgE anti-Ara h II.
To examine the potential role of T cells in the pathogenesis of peanut allergy. Peripheral blood mononuclear cells (PBMCs) from patients with peanut allergy, patients with asthma, and nonatopic normal control subjects were assessed for proliferation after stimulation with a 17 kd major peanut allergen (Ara h II), ovalbumin, casein, soy, and Candida albicans. That Ara h II and C. albicans induced significantly higher levels of proliferation than ovalbumin, casein, and soy. Because interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) play critical roles in IgE regulation, the production of these cytokines after stimulation with C. albicans and Ara h II. C. albicans stimulated similar levels of IFN-gamma in all three study groups. In contrast, after stimulation with Ara h II, culture supernatants from PBMCs of subjects with peanut allergy contained significantly lower levels of IFN-gamma than did the PBMCs of the two control groups (p = 0.02). More important, there was a significant (p = 0.05) inverse correlation between the serum IgE anti-Ara h II levels and IFN-gamma production by PBMCs from the respective peanut-allergic patients. IL-4 protein was not detected in culture supernatants of PBMCs stimulated with Ara h II. However, amplification of cytokine gene transcripts by polymerase chain reaction did demonstrate IL-4 expression in Ara h II-stimulated PBMCs from both patients with peanut allergy and control subjects. Conclusion is that the level of IFN-gamma production in response to Ara h II may be an important factor in determining the development of peanut-specific IgE responses (17).
(6). Other Laboratory Tests:- When evaluating patients with gastrointestinal symptoms, suspecting food hypersensitivities, a number of other standard laboratory studies might be useful. Patients with allergic eosinophilic esophagitis and allergic eosinophilic gastroenteritis have peripheral eosinophilia, and patients with severe allergic eosinophilic gastroenteritis might have anaemia, blood in the stool, and decreased serum protein, albumin and IgG levels (with preservation of IgM and IgA). Endoscopy and biopsy are the most definitive approaches for diagnosing many of the gastrointestinal food hypersensitivities and might help the differential diagnoses. Greater than 10-20 eosinophils per 40