D. M. Kemeny

Oral allergy syndrome (OAS): symptoms of IgE‐mediated hypersensitivity to foods

Eighty highly atopic patients were selected for study because they had either atopic eczema (fifty cases) or atopic reactivity to foods, as judged by a positive skin‐prick test (thirty cases). In all, sixty‐five out of eighty subjects (81%) described symptoms of some kind provoked by foods, but correspondingly positive skin tests were found in only half of these, thirty‐three out of eighty (41%). The symptoms experienced by thirty‐one of the thirty‐three patients with positive skin tests were immediate in onset (within 1 hr) and were at first confined to the upper gastrointestinal tract, the most frequent symptoms being oral irritation and throat tightness. In a proportion of these patients, further symptoms such as urticaria, asthma or anaphylaxis developed following the initial oral symptoms, which suggested the term‘oral allergy syndrome’. In the absence of the oral allergy, symptoms such as asthma, urticaria, migraine or eczema starting later than 1 hr after food were seldom associated with positive skin tests. In the oral allergy syndrome, the characteristic symptoms (strong association with positive skin tests and RAST, time of onset and sites at which symptoms are expressed) suggest a causative relationship between exposure to food antigens and specific IgE‐induced release of mediators. In cases of food intolerance that lack a characteristic symptom pattern and a positive skin test or radio‐allergo‐sorbent test, it seems appropriate to consider non‐IgE‐mediated causes.

The subclass of IgG antibody in allergic disease: II. The IgG subclass of antibodies produced following natural exposure to dust mite and grass pollen in atopic and non‐atopic individuals

In an attempt to understand the role of the different IgG subclasses in allergic disease, we have studied the subclass of IgG antibody to dust mite (HDM) and grass pollen (GP) produced as a result of natural exposure. Studies were carried out on 40 atopic children and 100 atopic adults who had never received immunotherapy. Thirty‐two non‐atopic adult controls were also studied. The specificity of the assay for IgG antibodies to dust mite was confirmed by inhibition with the homologous extract but not mite culture medium or fetal calf serum. IgG1 antibodies to HDM could be detected in most atopics (94%) and non‐atopics (97%), and similar results were obtained for GP (81% and 100%, respectively). IgG4 antibodies to HDM were detected in more atopics (66%) than non‐atopics (53%) and the difference was more marked for GP (72% vs. 19%). While the levels of IgG1 antibodies were not significantly different in the two groups, the levels of IgG4 antibodies were much lower in the non‐atopics (P < 0.001, Mann–Whitney U‐test). These data show that all subjects were capable of recognizing and mounting an IgG1 antibody response to these inhaled antigens. Atopic individuals differed from normal subjects in the frequency with which they made IgG4 antibodies in response to natural exposure to both dust mites and pollen.

Sub-class of IgG anti-bee venom antibody produced during bee venom immunotherapy and its relationship to long-term protection from bee stings and following termination of venom immunotherapy

The IgG sub‐class antibody response to bee venom in the four sub‐classes was investigated in ten patients during and after venom immunotherapy. All patients tolerated a bee sting challenge 1, 2 and 3 years after the start of treatment as well as 1 and 2 years after treatment was stopped. Anti‐phospholipase A2 (PLA2) antibodies were of IgG1 and IgG4 sub‐class and rose early in treatment, IgG1 anti‐PLA2 fell to pre‐treatment levels after 3 years in contrast to IgG4 anti‐PLA2 levels, which remained high during maintenance therapy and declined relatively little in the 2 years after the termination of treatment. This data shows that IgG4 antibodies are maintained in the absence of monthly maintenance injections and suggests that they may provide long lasting clinical protection from insect stings.

Genetic analysis of the linkage between chromosome 11q and atopy

Previous work has suggested that there is a genetic predisposition for the development of both asthma and atopy. A recent study has also shown that there is a striking link between chromosome 11q and the IgE response underlying asthma and rhinitis. To further assess the linkage between chromosome 11q and atopy, we have studied nine families of two and, in many instances, three generations with the index case having asthma and/or atopy. Using two restriction fragment length polymorphism probes associated with the regions 11q12‐q13.2, namely PYGM and INT2, we have been unable to confirm a significant link between this region of chromosome 11q and atopy as defined by a positive skin‐prick test and or a raised specific IgE and/or a raised total IgE.

Sub-class of IgG in allergic disease I. IgG sub-class antibodies in immediate and non-immediate food allergy

Abstract. Previous studies have suggested that, apart from IgE‐mediated reactions, some of the symptoms of food allergy may be caused by IgG antibodies to food proteins. This study was carried out to see if there were any distinctive features of the IgG sub‐class antibody response to dietary antigens which occurs in food allergic patients. IgG subclass antibodies were measured using a quantitative enzyme‐linked immuno‐sorbent assay (ELISA) to wheat gliadin, ovalbumin and bovine casein in twenty patients who had coeliac disease and in twenty‐eight egg allergic patients. These were compared with twenty‐one atopic dermatitis patients who did not have food allergy and twenty‐six healthy control subjects. Coeliac disease patients tended to have raised IgG antibody levels (especially IgG1) to all three antigens but these overlapped considerably with that seen in egg allergic and atopic dermatitis patients.

Use of the enzyme-linked immunosorbent assay for measurement of allergen-specific antibodies

A sensitive and specific enzyme-linked immunosorbent assay (ELISA) for allergen-specific IgG antibodies is described. Various solid-phase supports (microtiter plates), coating procedures, binding kinetics, and presentation of allergen in the assay were investigated. Using optimal conditions the indirect ELISA, in which the allergen is coated onto the well, was capable of detecting 2.4 ng/ml specific IgG antibodies to bee venom phospholipase A2(PLA2). The sandwich ELISA, in which the allergen was immobilized via specific antibody precoated onto the well, detected 0.24 ng/ml IgG antibodies to PLA2.

Skin and radioallergosorbent tests in patients with sensitivity to bee and wasp venom

Intradermal (ID) and prick tests with bee or wasp venom (Pharmalgen) have been performed on 102 subjects with a history of adverse reactions to stings and forty‐six control subjects giving no such history. Venom was diluted 100, 10 and 1 μg/ml for prick testing and 10‐2, 10‐2, 10‐3 and 10‐4%mUg/ml for ID injections.

IgE and IgG antibodies to bee venom as measured by a modification of the RAST method.

The radioallergosorbent test (RAST) has been widely used in studying allergy to hymenoptera stings, but with variable results. We report here a modification of the RAST method which in a total of 157 bee keepers and family members, gave a close correlation between a positive RAST, and a history of generalized (100%) or localized (95%) allergic reactions. There was no positive RAST among forty‐nine non‐atopic control subjects but a striking finding was that 58% of non‐allergic bee keepers had significant, but usually low, levels of IgE antibody to bee venom.

The relationship between anti‐IgE auto‐antibodies and the IgE response to wasp venom during immunotherapy

During immunotherapy with wasp venom, levels of venom‐specific IgE antibodies increase and then fall, whereas the concentration of IgG antibodies rises and then remains at a high level. Successful treatment is therefore associated with both increased concentrations of serum IgG and decreased serum IgE antibodies to venom. In this study we have investigated the possible role of auto‐antibodies in inducing the decrease in serum IgE antibody. Levels of auto‐anti‐IgE were measured by a radioimmunoassay. Anti‐IgE auto‐antibodies were not generated during immunotherapy and there was no significant difference in the levels of anti‐IgE auto‐antibodies between patients whose venom‐specific IgE antibody levels fell more than fivefold after immunotherapy and those patients in whom IgE antibody levels did not change significantly. We conclude that anti‐IgE auto‐antibodies do not play a part in IgE suppression induced by immunotherapy.

The use of monoclonal and polyspecific antibodies in the IgE sandwich ELISA

The use of antibody to link antigen to microtitre plates in the enzyme-linked immunosorbent assay (ELISA) has been extended to include mouse monoclonal antibodies and polyspecific rabbit antibodies. Small amounts of both reagents could be used. The capacity of the microtitre plate for the antibody was found to be critical and irradiated plates generally gave better results. Both rabbit anti-IgE conjugated to horseradish peroxidase, and monoclonal mouse anti-IgE with alkaline phosphatase-conjugated rabbit anti-mouse IgG could be used as detection reagents. Comparison with the radioallergosorbent (RAST) test showed a good agreement with the sandwich ELISA. The sandwich ELISA using polyspecific rabbit antibody was substantially more sensitive than conventional ELISA and also marginally more sensitive than RAST.