Toward an Understanding of Allergy and In-Vitro Testing

Toward An Understanding of Allergy and In-Vitro Testing

By Mary James, N.D.

SM Toward An Understanding of Allergy and In-Vitro Testing By Mary James, N.D.

Learning to recognize Food represents the largest anti- don’t will be discussed, or why a genic challenge facing the immune specific food elicits symptoms in and manage food system. Assuming complete diges- an individual at one point in time, allergies can go a long tion, an intact intestine, a sturdy yet appears to be well tolerated at constitution, and minimal anti- other times. We will examine why way in achieving better genic exposure such that the an individual sometimes feels bet- immune system is not over- ter from eating an allergenic food, clinical results whelmed, all goes well. Weaknesses but feels worse from eating it fol- with patients. in one or more of these areas, lowing a period of elimination. We however, can result in immune will look at why an allergy test attacks upon foods as if they were might be normal in an individual foreign invaders. A long list of who knows he experiences symp- conditions have been associated toms when ingesting certain foods, with food reactions, including or why an in-vitro test may show fatigue, migraines, irritable bowel elevated antibodies to foods in an syndrome, inflammatory bowel asymptomatic person. Finally, we disease, gallbladder disease, arthri- will discuss how to effectively man- tis, asthma, rhinitis, Attention age allergenic food elimination, Deficit Hyperactivity Disorder reintroduction and rotation. While (ADHD), enuresis, epilepsy, there are admittedly many useful eczema, psoriasis, aphthous ulcers, approaches to the diagnosis and and recurrent sinusitis, otitis media treatment of allergic disorders, the and other infections.(1) A patient following discussion will be limited with numerous and seemingly primarily to in-vitro assessment unrelated symptoms often moves and dietary management. from doctor to doctor in search of a diagnosis. When the inflammato- The Immune System ry response to an allergen takes Before embarking on a discussion hours or days to develop, the of allergy, let’s start with a few relationship between foods and basics of the immune response. symptoms is often hard to pin The following overview will provide down. Learning to recognize and a foundation for our discussion. manage food allergies can go a long way in achieving better clinical The principle cells of the immune results with these patients. The system are lymphocytes, plasma intent of this paper is to provide cells and macrophages, collectively such an understanding. organized into lymphoid tissue. Lymphocytes can be further divid- In this paper, we will focus on IgE- ed into B-cells and T-cells. and IgG-mediated immune reac- Interestingly, these cell names were tions. Reasons why some individu- based on parts of a chicken, as 2 als develop allergies while others studies of the thymus (T) and the bursa of Fabricius (B) (a lymphoid reactions to foods and other sub- organ near the cloaca) brought stances. Examples include lactose about the first understanding of intolerance, pharmacological their respective immunological responses to alkaloids in foods functions. The chief role for B-cells such as solanine (potato family), is the provision of humoral immu- salicylate sensitivity, and lectin nity. Upon exposure to an antigen, reactions, in which dietary lectins B-cells proliferate and evolve to interact with surface antigens on antibody-synthesizing plasma cells cells, causing them to agglutinate. that then produce antigen-specific Bacteria and bacterial toxins may immunoglobulins of different isotypes, called IgM, IgG, IgE, IgD and IgA. T-cells, on the Non-immune Mediated Reactions to Foods other hand, provide cell-mediated immunity. • Lactase deficiency (dairy) ➔ bloating, flatulence, diarrhea, abdominal pain • Spoilage or contamination of food by bacteria (Proteus) or heat-stable toxins There is considerable interaction (tuna, bonita, mackerel) ➔ itching, rash, vomiting, diarrhea among components of the • Gallbladder disease ➔ abdominal pain (RUQ), nausea, flatulence, aggravation by fats immune system. Subsets of T- cells, function as: helper T-cells, • Vasoactive amines -phenylethylamine (chocolate, aged cheese, red wine) ➔ migraine which stimulate B-cell activity; -tyramine (cheddar cheese, French cheeses, brewer’s yeast, chianti, canned fish) ➔ or as suppressor T-cells which migraine, erythema, urticaria, hypertensive crises in patients on MAO inhibitors suppress both humoral and cell -histamine (fermented cheese, fermented foods (e.g. sauerkraut), pork sausage, mediated immune responses. canned tuna, anchovies, sardines) ➔ erythema, headache, hypotension Macrophages are released from -histamine-releasing agents (shellfish, chocolate, strawberries, tomatoes, peanuts, ➔ the bone marrow as monocytes, pork, wine, pineapple) urticaria, eczema, pruritis and develop into macrophages • Food additives (e.g. tartrazine, FD&C Yellow No. 5, sodium benzoate) ➔ hives, upon entering tissue. rash, asthma Macrophages serve to present • Sulfites (salad bar lettuce, shrimp, dried fruits and vegetables, wine, beer) ➔ asthma antigen to both T- and B-cells, or anaphylaxis, loss of consciousness as well as to clear antigen/anti- • Monosodium glutamate (Chinese and Japanese dishes) ➔ headache, facial tension, body complexes from the circu- sweating, chest pain, dizziness lation. The efficiency of this • “Nightshade” alkaloids (potatoes, tomatoes, eggplant, peppers, tobacco) ➔ joint function is critical in controlling pain food-induced hypersensitivity ➔ reactions, as we will discuss. • Hypoglycemia Fatigue, palpitations, shakiness, cognitive impairment, mood swings, poor memory, blurred vision, anxiety, dizziness, headache • Lectin reactions (wide variety of foods) ➔ wide variety of symptoms, depending on Getting Our Terms blood type compatibility. (Refer to: Eat Right 4 Your Type, by Peter D’Adamo, N.D.) Straight The terms "food intolerance," "allergy" and "hypersensitivity" are cause gastrointestinal and systemic often used interchangeably. For reactions, such as in scombroid clarification, it’s useful to poisoning from the ingestion differentiate among them… of contaminated tuna. Vasoactive amines (epinephrine, norepineph- Intolerance rine, tyramine, dopamine, histamine and 5-hydroxytryptamine) The term "intolerance" generally are found in bananas, tomatoes, applies to non-immune mediated avocados, cheeses, pineapples and 3 wines, and can contribute to •Type II immune reactions involve symptoms such as migraine antibody-mediated destruction of headache. Sulfite, used as a tissue following adherence of preservative in foods such as let- foreign material. This reaction is tuce, shrimp, dried fruit and wine, often referred to as a "cytotoxic can cause asthma and urticaria.(2) reaction." Examples of Type II Some compounds, such as alco- reactions include penicillin reac- Any food eliciting an hol, may even induce histamine tions and those resulting in red responses, although the reaction is cell or platelet destruction. adverse reaction should not immune mediated. •Type III reactions are mediated ideally be avoided, no Because of the conspicuous by mixed immunoglobulins, but matter what the relationship between ingestion primarily IgG. Complexes com- of the food and the onset of posed of antigen and antibody mechanisms, and symptoms, such reactions are fre- activate complement and cytokines quently mistaken for allergy, yet an in the body, resulting in an inflam- careful investigation allergy test may be negative for that matory response. Type III reactions aimed toward the food. Any food eliciting an adverse constitute the basis of "delayed- reaction should ideally be avoided, onset" food allergies. Symptoms causative factors. no matter what the mechanism, are delayed because of the time and careful investigation aimed required for the formation of toward the causative factors. complexes. These reactions will also be discussed in more detail.

Hypersensitivity •Type IV refers to cell-mediated Although the use of the term immune reactions, where T-cells "hypersensitivity" is sometimes act as the primary players. T-cells reserved only for Gell and Coombs’ become cytotoxic cells when acti- classification of Type III, IgG- vated by antigen, capable of killing mediated reactions, traditionally viruses, bacteria, tumor cells or the term is applied to all four types other target cells. Type IV reactions of tissue injury. Types I through IV play a significant role in tuberculo- all depend upon the interaction of sis, mycotic and viral infections, antigen with humoral antibody, contact dermatitis and allograft and result from an excessive rejection. These reactions may also immune reaction to antigen, be involved in some food allergies, leading to gross tissue changes such as protein-losing entero- and symptoms. pathies and celiac disease.

•Type I reactions are mediated by Allergy IgE antibodies, and are character- The definition of the term "allergy" ized by the release of histamine is much debated. Although many and other chemical mediators traditional allergists strictly reserve upon exposure to an allergen. the use of the term for Type I IgE- Type I reactions are responsible mediated reactions such as hay for "immediate-onset" allergies, fever, a more general definition of such as hay fever or anaphylaxis. "allergy" refers to any acquired They will be discussed in more hypersensitivity to an antigen that detail below. results in harmful immunologic 4 consequences. For our purposes, bronchial and cutaneous allergies we will apply this broader defini- show a familial tendency. This is par- tion to both Type I and Type III ticularly true for asthma, hay fever, immune reactions. recurrent rhinitis and bronchitis, and eczema; when present in a parent, Immediate-Onset IgE there is an increased prevalence of Reactions the same disorder in the child.(3) If neither parent is allergic, a patient’s When an antigen attaches to IgE IgE antibody levels may symptoms are less likely to reflect an antibodies already stationed on a IgE-mediated reaction. IgE allergies drop with avoidance mast cell or basophil, pre-formed are in place for life. Antibody levels bundles of histamine are released. may drop with avoidance of expo- of exposure, but Inhalation of antigens usually sure, but re-exposure will quickly leads to the symptoms we com- re-exposure will quickly result in the mobilization of IgE anti- monly associate with "allergy" bodies and the subsequent release of result in the such as sneezing, itching of the histamine. palate or ears, runny nose, itching mobilization of and tearing in the eyes, and fatigue. As mentioned above, IgE-mediated Ingestion of an antigen may lead to antibodies and the food allergies are usually easy to symptoms such as asthma, an itchy spot because of the immediate subsequent release rash, angioedema or gastrointesti- appearance of symptoms. Common nal symptoms such as abdominal culprits include peanuts and shell- of histamine. cramps and diarrhea. fish. Sensitivity to these substances is so extreme in some cases that Chronic IgE allergies may manifest anaphylaxis may result from the as sinusitis, recurrent ear or upper mere inhalation of vapors from respiratory infections, mouth food or contact with the skin. breathing and post-nasal drip. Needless to say, management of "Allergic shiners" under the eyes these allergies requires strict avoid- and a white line across the nose, ance of the offending substance. from repeated upward wipes of the IgE reactions triggered by inhalants nose with one’s hand, are common often show a seasonal pattern, with signs of IgE-mediated allergies in reactions to tree pollens children, although these signs have typically occurring in the spring, also been observed in individuals grass pollens in late spring and early with IgG allergies. Severe Type I summer, and weed pollens in late reactions may include anaphylaxis. summer and early fall. Reactions to The allergic reaction occurs imme- dust mites often appear in the win- diately upon exposure to the anti- ter, with the onset of home heating. gen (usually less than two hours); Allergy testing during a sympto- consequently, the person experi- matic period can help to identify encing the reaction usually easily the responsible antigens. Allergies recognizes the link between aller- to pet dander can occur at any gen and symptom. time, upon exposure. Specific IgE-mediated allergies are not inherited, although Type I aller- Mold and Fungi Reactions gic diseases in general tend to run Mold allergies tend to coincide in families, and end-organ sensitivi- with wet months that feature ties associated with nasal, above-freezing temperatures, e.g. 5 December through March in typically are Type III and IV and California, summer in the mid- involve IgG antibodies. Symptoms west, or year-round in Florida. Very may include flu-like illness with dry states, such as Arizona or fatigue, rash, muscle and joint Nevada, are unfortunately not pain, headache, fever and exempt from inhalant mold aller- nightsweats. Fungal colonization A food allergy test can gies, as the moisture in air condi- may be life-threatening in immuno- be most clinically tioning units invites the growth of compromised individuals. mold which then becomes dissemi- useful for measuring nated throughout the living space. Avoidance of allergen, in the case Delayed-Onset IgG IgG antibodies involved of molds and fungi, can be Reactions in delayed-onset extremely challenging since these Type III reactions involve the substances are so ubiquitous in the formation and deposition of Type III reactions. environment. Common food antigen/antibody (Ag/Ab) com- sources include fermented cheese, plexes, mostly involving IgG. In wine, beer and bread. Other com- contrast to the immediate IgE mon, but less suspected sources histamine-mediated reactions, include tea, processed foods, these reactions are delayed, since dough conditioner, commercial they involve the gradual formation fruit juices, citric acid, malt flavor- of immune complexes. Because ings, chocolate, soy sauce, tomato these reactions are delayed by products (crushed and left to sit hours or even days following the for better flavor), Lactaid and B exposure, the relationship between vitamins. Fungal colonization of food and symptoms is much more the skin or mucous membranes difficult to spot. It is these reac- represents a third source of expo- tions for which a food allergy test sure which may serve to amplify measuring IgG antibodies can be reactions to other fungi in the envi- most clinically useful. ronment. Since different fungi from different sources share common IgG-mediated reactions typically surface proteins, the immune result from exposure to an excess response to fungi may cross-react. of antigen over an extended period As a result, correcting conditions of time. In the case of food allergy, such as dandruff, athlete’s foot increased intestinal permeability and Candida overgrowth often coupled with repetitious ingestion helps to lessen reactions to the of particular foods causes excessive other sources. antigen to be presented to the immune system. Formation of Such reactions are all primarily insoluble antigen/antibody com- IgE-mediated and feature the plexes results in the activation of symptoms commonly associated complement and the subsequent with histamine, such as sneezing, respiratory burst in neutrophils, runny nose and asthma. More the release of proteolytic enzymes, severe illness may result when an mast cell mediators and vasoactive individual is exposed to a much peptides, and the aggregation of larger number of fungal particles, platelets. Although complement such as in occupational exposures. stimulates inflammation, it also Due to the massive amount of functions to prevent the progres- 6 antigen exposure, these reactions sion from small complexes to larger ones, a factor that helps may NOT elicit symptoms, despite minimize the severity of symptoms. the fact that an immune reaction is Macrophage activity triggers the occurring. An overload of antigen, release of inflammatory mediators however, will saturate the such as interleukin-1, tumor necro- macrophages’ capacity, resulting in sis factor, reactive oxygen species the circulation of complexes and and nitric oxide. their deposition in tissue. Immune compromise may lead to the same Symptoms are typically delayed end, resulting in symptoms. (This in onset, by hours or days, and process is quite different from the vary, not only according to the "loaded gun" IgE response which is specific nature of the immune elicited with every exposure.) This complex, but also according to "overload" phenomenon may help the tissue in which the complexes explain why reducing exposure to are deposited. Headache, vasculitis one allergen may result in an indi- or hypertension may result from vidual being better able to tolerate deposition in the vascular space; other allergens. Unlike Ag/Ab inter- asthma, alveolitis or recurrent actions, macrophage clearance is infection may result from deposi- NON-specific. This means that tion in respiratory tissue, dermato- ANY reduction in demand on logic changes from deposition in macrophages (including non-aller- the skin, and joint pain from gic conditions such as infection or deposition of complexes in the joint xenobiotic exposure) may serve to space. Symptoms such as rhinitis or reduce symptoms and allow other angioedema may also occur, since reactive foods to be eaten. Antigen “overload” two elements in the complement cascade (C3 and C5) are capable This concept of "total load" can- may help explain why of inducing histamine release. Any not be overemphasized. It was not system may be affected and any until the middle of the last century reducing exposure to one symptom is possible, depending on and the growth of the industrial allergen may result in an an individual’s susceptibilities. revolution that the diseases which Reactions may last for days. we now call atopic allergic diseases, individual being better able were recognized as entities. (4) to tolerate other allergens. Hypersensitivities involving Immune Competency and bronchial symptoms and asthma "Total Load" nearly doubled during the 1980s Although an immune interaction and early 1990s.(5) Air pollution, between antibody and antigen including the contribution by diesel occurs every time an individual is exhaust particle emissions, has exposed to an allergenic food, the been shown to enhance both nasal presence and the degree of symp- IgE production and the expression tomatology depends upon the sol- of Th2 cytokines (6), and may ubility of complexes and the reticu- serve as a carrier for pollen and loendothelial system’s ability to other compounds. clear them. Macrophages pick up Ag/Ab complexes immediately, but Food allergies can develop at any have a finite capacity. With an effi- point in one’s life, but an individ- cient immune response, the half- ual may also be born with them. life of a complex may only be a few Such allergies are usually to foods minutes, and exposure to allergens that the mother consumed fre- 7 quently during her pregnancy, symptoms, yet allergies exist, a test although the antibodies are the can help to identify those foods baby’s own. Since maternal dietary which to some degree are stressing proteins are capable of reaching the immune system. If a person is amniotic fluid, and since the fetus is allergic to numerous foods, the capable of mounting antibody and test can also help provide a start- other immune responses as early as ing place, in terms of elimination. the tenth week of gestation, it is possible that fetal sensitization to these In-Vivo Skin Testing proteins begins as early as the first Type I allergies are often trimester of pregnancy.(7) Maternal diagnosed with skin prick testing, IgG antibodies traverse the placenta or with intradermal testing, often during pregnancy, but levels of these employed as a follow-up to a in the infant are typically down by 3- negative skin prick test. Advantages 6 months after birth.(8) Dietary of skin testing include rapid results, proteins from the mother’s diet good sensitivity, and the ability to are also transferred to breast milk. test any antigen. Disadvantages While a certain amount of antigen include the discomfort inherent in passage into the breast milk is prob- the procedure, ably important for the development possible danger of anaphylaxis,(9) of the infant’s tolerance the contraindicating effects of An allergy test to foods, excessive exposure can medications such as anti-hista- result in hypersensitivity. Breast-fed mines, decongestants, beta should always be infants whose mothers take dietary blockers, bronchodilators and theo- precautions during lactation are assessed in conjunction phylline, and occasional interfer- observed to have a markedly reduced ence from skin disease. Since skin with a patient’s incidence of atopic eczema.(7) testing only reflects IgE-mediated reactions, it also cannot inform clin- clinical picture. Unlike IgE allergies, those icians as to the potential for the mediated by IgG may be cured, delayed hypersensitivity reactions following a period of avoidance responsible for such a wide range of and attention to underlying con- symptoms seen clinically.(10) tributing factors. Although a food may be tolerated at some point on In-vitro Antibody a limited basis, the immune system Measurement "holds a grudge," in a sense. The measurement of antigen-spe- Because the hypersensitivity is cific antibodies is a useful tool for recorded in the body’s "memory assessment of allergies, particularly cells" (antigen-stimulated lympho- to foods. One study of young chil- cytes), the response may be reacti- dren found that 62.5% of children vated if exposure again becomes with symptoms had specific IgG excessive or too frequent. antibodies and 22.9% had specific IgE antibodies, while the children DIAGNOSIS without symptoms of food allergy An allergy test should always be had neither.(11) assessed in conjunction with a patient’s clinical picture. If an indi- Three widely used methods for vidual’s immune clearance mecha- measuring specific antibodies 8 nisms are effective in averting include ELISA, MAST and RAST/RASP. ELISA (enzyme-linked ing can provide a starting place for immunosorbent assay) can detect trial elimination programs. As a either IgG or IgE antibodies. MAST screen for an asymptomatic individ- and RAST (radioallergosorbent ual, in-vitro testing may reveal food procedure) measure IgE antibod- allergies which are currently being ies, although MAST testing for IgG effectively managed by the immune antibodies is currently being devel- system (hence, no symptoms), but oped. Some laboratories measure which could manifest symptomati- In-vitro allergy tests only IgG4 for foods; however, cally in the future, in the event of measurement of total IgG increased immune burden. offer the advantages of is recommended. Occasionally, a test will exhibit "across-the-board" low-level IgG convenience, safety (no Although all IgG subclasses are reactivities for an individual. Clinical danger of anaphylaxis), involved in the immune response, observation has suggested the pos- IgG1 is thought to be the main sibility of a chronically "leaky gut" lack of interference by instigator of inflammation. The in such situations, and the con- role of IgG4 in food allergy has comitant immune reaction to a medications or skin been debated. IgG4 is unable to large number of absorbed antigens. condition, and good activate complement, so does not contribute to a true inflammatory Disadvantages of in-vitro testing reproducibility. reaction. It is, however, able to include the requirement of serum precipitate the release of histamine collection, the sometimes lengthy from basophils (12), which might incubation and the possibility of partially explain the elevated levels some false negatives for IgE, which observed in atopic individuals and may result from a number of fac- amelioration of symptoms upon tors. Antibodies that are directed removal of the "positive" foods toward altered forms of antigen not from the diet.(13) At the same time, used in the test, e.g. cooked, it has been suggested that IgG4 spoiled or processed foods, might may function as a "blocking" anti- go undetected. False negatives may body to allergic reactions, particu- also follow immunotherapy, a larly since levels tend to increase result of IgG "blocking" antibody dramatically following successful production. (This is one of the immunotherapy for IgE-mediated mechanisms behind immunothera- pollen allergies.(14) Although IgG4 py’s effectiveness for IgE-mediated can induce histamine release, its allergies; antigen now preferentially release appears to be more delayed binds to IgG, rather than IgE, so and the reaction less acute than in that the immediate and acute hist- the Type I IgE reactions. amine reaction is prevented.) Finally, with the possible exception In-vitro tests offer the advantages of anaphylaxis-inducing allergens, of convenience, safety (no danger specific immunoglobulins tend to of anaphylaxis), lack of interfer- gradually diminish in response to ence by antihistimines or skin con- antigen elimination. Although the dition, and good reproducibility. half-life of IgE antibodies is only 3 In -vitro also allows the use of par- days and the half-life of IgG 23 allel controls with each run. A pos- days, absorbed antigens which have itive reaction on an in-vitro test sig- been sequestered by the liver may, nifies allergy in that individual. For in some cases, be slowly released the "global reactor," in-vitro test- over several months, resulting in 9 some persistent antibody ticular food may not, in fact, corre- production. The levels, however, late with improvement in, or aggra- will still decline over time, barring vation of, an individual’s level of any new exposure. Because foods reactivity. Even the broad cate- such as wheat, dairy and corn are gories of 0-3+ should be evaluated widely used as additives in against the patient’s clinical pic- processed foods or cosmetics, IgG ture. A 3+ IgG reaction will gener- levels are more likely to persist in ally imply a stronger immune reac- an individual who mistakenly tion (or a more severe allergy) than presumes that he has completely a 1+ reaction. However, that 3+ eliminated the foods. IgE antibod- reaction may never manifest as ies to seasonal allergens may be symptoms in a person whose sys- undetectable if measured during an tem is effectively neutralizing asymptomatic period. immune complexes, while a 1+ reaction may result in debilitating Interpreting the In-Vitro symptoms in a person whose retic- Test ulendothelial system is over- It should be noted that in-vitro whelmed. In other words, the best antibody tests are semi-quantita- use of the test is to identify reactive tive. All procedures involve the substances which can then be binding of specific anti-food anti- avoided or rotated in a clinical bodies to an antigen that is already trial. bound to a solid phase, e.g. a plate or test tube. Each procedure Elimination Diets includes a tag, or signal, which is Elimination and reintroduction of quantitated. The tag used in the foods is an invaluable means of RAST is a radioactive isotope, establishing a relationship between In-vitro antibody tests while MAST uses a luminescent sig- a symptom and a particular food. nal. In the ELISA test, the tag is an The typical protocol involves the are semi-quantitative. enzyme that induces a color elimination of all possibly aller- change which is then read photo- The best use of genic foods (commonly the routine metrically as "optical densities." foods in one’s diet) for 1-2 weeks the in-vitro allergy The more intense the color change, and, assuming any clinical the higher the concentration of improvement during this time, the test is to identify specific antibodies. Because of gradual reintroduction of one food inherent imprecision in the multi- reactive substances every 2-3 days. If a food in one step processes used in these proce- meal fails to produce symptoms, which can then be dures, there will always be some then a larger amount is eaten in natural "drift" in the quantifica- the next couple of meals. If symp- avoided or rotated in tion. It is for this reason that toms reappear within the 2-3 days reporting of broad categories for a clinical trial. of repeated ingestion of a food, reactivity, e.g. 0-3+, has become an that food is regarded as allergenic, industry standard. and eliminated from the diet. If no symptoms are induced, the food is Literal reliance upon the larger now included in the hypoallergenic optical density numbers (in the diet, and the next food is tested in case of ELISA) can be misleading, the same manner. as a follow-up test featuring higher or lower optical densities for a par- Needless to say, this process may 10 take several weeks to complete, Inhalant allergies are most often depending upon the number of treated with a combination of foods tested, and it requires avoidance, where possible, and more than a modicum of self- immunotherapy, which consists of discipline. The results, however, injections of serially increasing con- prove invaluable. The patient is centrations of antigen. As antigen not only able to ascertain which is introduced into a patient’s sys- foods produce which symptoms, tem, the immune system gradually but the clinical experience of develops a mixed IgG response to improvement on the elimination it, although never enough to cause diet and the aggravation upon tissue damage. The IgG antibodies ingestion of a food, often serves are thought to block the more to provide the needed incentive severe IgE reaction, and symptoms usually abate within a few weeks. for the subsequent long-term Combining a elimination or rotation of offend- Standard immunotherapy is not ing foods. The process assists in used for the desensitization to preliminary in-vitro revealing the NON-immune medi- foods and molds because the large ated reactions as well. As discussed amount of antigen exposure from test with an natural sources is usually already earlier, a relationship between food elimination diet and symptom does not automati- so high that severe reactions are cally mean "allergy." likely to be induced. It should be represents the most noted that, although IgE antibod- There are a few disadvantages to ies to a substance remain in the efficient approach of system, an IgE blood test may fail relying solely on the elimination all, and improves diet for diagnosis. The length of to pick them up following treat- time and discipline required are ment, due to the competitive patient compliance. mentioned above. Sub-clinical inhibition by IgG. This significant hypersensitivities will not be detect- a decline, however, appears to ed. Finally, the possibility exists occur only after about two years that some of the foods consumed of hyposensitization.(15) as components of the "hypoallergenic" diet are antigenic for a given individual. In this case, ameliora- Enzyme-potentiated tion of symptoms on the diet does desensitization not occur, and the false conclusion Enzyme-potentiated desensitization is reached that foods play no part (EPD) also utilizes the periodic in the patient’s illness. Combining injection of antigen into the a preliminary in-vitro test with an patient’s skin, but the amount of elimination diet represents the antigen compared to standard most efficient approach of all, and immunotherapy is exceedingly improves patient compliance. small. Furthermore, the antigen is accompanied by the enzyme TREATMENT beta-glucuronidase which helps to activate T-suppressor (CD8) cells. Following is a brief discussion of a Unlike immunotherapy, IgG levels few of the most popular methods do NOT rise in response to the for managing allergies. treatment, although tolerance develops. Injections are adminis- Immunotherapy tered every two months and in most cases can eventually be (Hyposensitization) 111 spaced further apart, assuming greater likelihood that sensitivities improvement. EPD is used for food to oyster, scallop and squid (other and mold allergy and is preferred members of the "mollusk" family) by many physicians for treatment might be present. At the same time, of inhaled allergens, as well. such cross-reactions have been observed to be relatively infrequent, Medications and patient compliance is always a Other standard treatments for consideration. Care must also be inhalant allergies include the use taken that suspected foods are not of anti-histamines, decongestants, inadvertently consumed while hid- glucocorticosteroids, and sodium den in other foods, e.g. eggs con- cromoglycate. This last one serves tained in mayonnaise. to block mast cell degranulation, eosinophil and neutrophil chemo- Eliminating the antigenic food taxis and mediator release; howev- provides the immune system a rest. er, it is poorly absorbed orally, Levels of antibodies gradually so must be taken frequently in decline, immune complexes are order to maintain adequate cleared, and symptoms improve. mucosal concentrations. Quercitin Lesser reactive foods are often is a natural bioflavonoid with tolerated in the beginning if eaten similar activity.(16) All of these no more often than every four medications are merely palliative, days or so; however, this tolerance Eliminating the but of course can make a world varies between individuals, and in of difference in a patient who is the more symptomatic patient antigenic food experiencing paroxysmal sneezing even foods with 1+ reactivities or a frightening bout with asthma. may have to be temporarily provides the immune removed from the diet in order to system a rest. Levels of Allergen Elimination improve clinical outcome. The most important component antibodies of any allergy program is the reduc- Antigen/Antibody gradually decline, tion of exposure to the offending Equilibrium agent. As long as exposure is main- One of the most important deter- immune complexes are tained, antibodies will continue to minants of the pathogenicity of be produced and the immune sys- cleared, and the Ag/Ab complex and the clinical tem "primed" to react. IgE-mediat- course of the patient is the equilib- symptoms improve. ed allergies tend to be "fixed," thus rium between antigen and anti- avoidance is usually life-long. In body. At equivalent concentrations contrast, the IgG-mediated allergies (also called the "zone of equiva- may be reversed over time. Reactive lence"), complexes can grow to foods are ideally eliminated from enormous size. The larger and the diet for a minimum of three more numerous the complexes, the months, particularly those that more likely they are to overwhelm evoke the most severe symptoma- the reticuloendothelial system and tology or the highest scores on an deposit in bodily tissues. in-vitro test. Ideally exposure to Individuals with IgG allergies often foods within the same food family have the paradoxical experience of of a reactive food should be feeling immediately better, rather reduced as well. A sensitivity to than worse, after consuming an clam, for example, may indicate a allergenic food. What is happening 121 here is a shift into the zone of Plasma cells retain a memory of "antigen excess."(17) In this zone, that sensitivity, and new antibodies complexes become more soluble could be produced with any expo- and symptoms may diminish, that sure. Only a trial reintroduction is, until more antibody is produced will answer that question. If no and the "zone of equivalence" is symptoms are elicited when the

Antigen Excess Zone of Equivalence Antibody Excess

again reached, producing more food is reintroduced, the food can symptoms. Eating more of the usually be replaced into the diet, food once again brings relief, but ideally on a rotational basis. perpetuating a vicious cycle of Repetitive exposure to a food usu- addiction that is difficult to break. ally contributes to the development Following 7-10 days of strict of hypersensitivity in the first place, elimination of a reactive food, an thus a return to the same frequen- individual moves into a zone of cy of exposure often brings with it One of the "antibody excess." With less anti- an eventual return of symptoms. most important gen on board, complexes reduce in size and number, and symptoms determinants of the diminish. During this period, he Other Considerations pathogenicity of the or she is extremely sensitive (hence In the case of reactivity to molds, the conspicuous and diagnostic yeast or fungi, it is often useful to clinical course of aggravation from reintroductions treat any existing infections. of offending foods at this point), Examples include ringworm, ath- the patient is the and should stay with the elimina- lete’s foot or jock itch, as well as equilibrium between tion diet for three or more months, vaginal or intestinal yeast over- while antibody levels drop. growth. Doing so may help to antigen and antibody. eliminate cross-reactivity reactions After this point, a follow-up in- and lower the overall burden on vitro test might well show lower the immune system. reactivities for those foods that have been avoided. This fact does Because IgG allergies can be not guarantee that the food will be established as a result of the tolerated when reintroduced. translocation of food antigens 13 across a permeable gut wall (18), imbalances will greatly help to attention to gut repair is a prereq- reduce the likelihood of developing uisite for preventing further prob- additional allergies. lems. It is not uncommon for a person who is eating soy foods, Finally, it’s worth noting that e.g. as a substitute for foods such adjunctive nutritional support for as cow’s milk and wheat, to sud- the immune system, as well as Correcting imbalances denly find herself now unable to selective botanicals, homeopathic tolerate soy after a few months. remedies or acupuncture, may con- in the gastrointestinal Evaluation of intestinal permeabili- tribute significantly to the reduc- flora and providing ty as well as a comprehensive stool tion in immune sensitivity and the analysis can serve to establish the inflammatory response. nutritional support for presence of "leaky gut" and con- tributing factors such as maldiges- Acknowledgements: Special thanks the immune system can tion, malabsorption, imbalances in to Vincent Marinkovich, M.D., greatly help reduce flora, secretory IgA deficiency and (Diplomat, American Board of mucosal injury due to infection or Allergy and Clinical Immunology) immune sensitivity. agents such as non-steroidal anti- for his generous contribution of inflammatories. Correcting any information on the subject.

14 REFERENCES 1) Gaby AR. The role of hidden food allergy/intolerance in chronic disease. 10) El Rafei A, Peters SM, Harris N. Bellanti JA. Diagnostic value of IgG4 mea- Alt Med Review 1998;3(2):90-100. surement in patients with food allergy. Ann Allergy 1989;62:94-99.

2) Buckley RH, Metcalfe D. Food allergy. JAMA 1982;248:2627-31. 11) Hofman T. IgE and IgG antibodies in children with food allergy. Rocz Akad Med Bialmyst 1995;40(3):468-473. 3) Gerrard JW, Ko CG, Vickers P. The familial incidence of allergic disease. Ann All 1976;36:10. 12) Vijay HM, Perelmutter L. Inhibition of reagin-mediated PCA reactions in monkeys and histamine release from human leukocytes by human IgG4 sub- 4) Mygind N. History of Allergy. In: Essential Allergy—An Illustrated Text for class. Int Arch Allergy Appl Immunol 1977;53:78-87. Students and Specialists. Boston: Blackwell Scientific Publications, 1986:1-9. 13) Gwynn CM, Ingram J. Bronchial provocation tests in atopic patients with 5) Chandra RK. Food allergy and food intolerance: lessons from the past and allergen specific IgG4 antibodies. Lancet 1982;1:254-256. hopes for the 21st century. In: Somoyogi JC, Muller HR, Ockhuizen T, editors. Food allergy and food intolerance. Nutritional aspects and developments. Bibl 14) Van der Giessen M, Homan WL, van Kernebeek G, et al. Subclass typing Nutr Dieta 1991;48:149-156. of IgG antibodies formed by grass pollen allergic patients during immunotherapy. Int Arch Allergy Applied Immunol 1976;50:625-639. 6) Casillas AM, Nel AE. An update on the immunopathogenesis of asthma as an inflammatory disease enhanced by environmental pollutants. Allergy 15) Szymanski W, Chrek-Borowska S, Obrzut D. IgG, IgA, IgM and IgE serum Asthma Proc 1997 Jul-Aug;18(4):227-33. levels in asthmatic patients sensitive to house dust and mite allergens after two-year specific immunotherapy. Arch Immunol Ther Exp (Warsz) 7) Chandra RK. Food allergy and food intolerance: lessons from the past and 1984;32(4):381-7. hopes for the 21st century. In: Somoyogi JC, Muller HR, Ockhuizen T, editors. Food allergy and food intolerance. Nutritional aspects and developments. Bibl 16) Middleton E Jr , Drzewiecki G. Flavonoid inhibition of human basophil Nutr Dieta 1991;48:149-156. histamine release stimulated by various agents. Biochem Pharmacol 1984 Nov 1;33(21):3333-8. 8) Host A, Husby S, Gjesing B, Larsen JN, Lowenstein H. Prospective estima- tion of IgG, IgG subclass and IgE antibodies to dietary proteins in infants with 17) Randolph TG. Specific adaptation. Ann Allergy 1978;40:333-345. cow milk allergy. Levels of antibodies to whole milk protein, BLG and ovalbu- min in relation to repeated milk challenge and clinical course of cow milk 18) Andre C, Francoise A, Colin L. Effect of allergen ingestion challenge with allergy. Allergy 1992 Jun;47(3):218-29. and without cromoglycate cover on intestinal permeability in atopic dermatitis, urticaria and other symptoms of food allergy. Allergy 1989;44(9):47-51. 9) Sampson HA, Metcalfe DD. Food allergies. JAMA 1992;268(20):2840- 2844.

15 Great Smokies Diagnostic Laboratory SM 63 Zillicoa St., Asheville, NC 28801-1074 800-522-4762 E-mail: [email protected] www.greatsmokies-lab.com

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This information is for the sole use of a licensed health care practitioner and is for educational purposes only. It is not meant for use as diagnostic information. All claims submitted to Medicare/Medicaid for GSDL laboratory services must be for tests that are medically necessary. "Medically necessary" is defined as a test or procedure that is reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member. Consequently, tests performed for screening purposes will not be reimbursed by the Medicare program. Physicians may deem it medically necessary to order a single test or a portion of a profile.

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