M. H. Lessof

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.

INTESTINAL PERMEABILITY IN PATIENTS WITH ECZEMA AND FOOD ALLERGY

Polyethylene glycol (PEG) was used as a probe molecule to investigate intestinal absorption in eight patients with eczema and evidence of food allergy and ten with eczema alone. In both groups absorption of molecules of larger molecular weight was greater than in normal subjects but absorption of molecules of low molecular weight was normal. There was no difference in absorption between eczema patients with or without food allergy. These results suggest that there is an intestinal mucosal defect in eczema which exists whether or not there is coexistent food allergy. Half the patients with eczema alone and two of the eight with food allergy had more of the large molecular weight PEG recovered in their urine in the second 12 h after ingestion than in the first 12 h. This could be the result of abnormal permeability in the more distal small bowel or even in the colon.

ROLE OF BRONCHIAL IRRITANT RECEPTORS IN ASTHMA

Sulphur dioxide inhaled at low concentration had no detectable effect on forced expiratory volume in one second in non-asthmatic atopic controls, but it induced asthma and increased bronchial reactivity in nine symptomless atopic and non-atopic asthmatic patients. This increased reactivity was inhibited by sodium cromoglycate (SCG) and partly inhibited by atropine. This suggests that SCG, in addition to its ability to stabilise mast cells, may also act on bronchial irritant receptors or directly on smooth muscle in asthmatic patients.

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.

Antibodies to purified bee venom proteins and peptides: I. Development of a highly specific RAST for bee venom antigens and its application to bee sting allergy

IgE antibodies to purified proteins and peptides from honeybee venom have been measured by the RAST. Trace amounts (less than 0.1%) of the major venom protein phospholipase A2 (PLA2) grossly distorted the measurement of IgE antibody to the other venom proteins, acid phosphatase (Acid P) and hyaluronidase (HYAL), and overemphasized their importance. Reduction of antigen coupled to the cellulose paper discs, which were used in the assay, diluted out the contaminating PLA2 without apparent loss in sensitivity. The reduction of disc-bound antigen increased the competition between IgE and IgG antibodies but did not affect measurement of IgE antibodies in sera taken from 35 untreated patients who had a history of general allergic reactions to bee stings. In 54% of sera from bee venom--allergic patients, the greatest IgE antibody response was to PLA2. In all, IgE antibodies to PLA2 were present in 91% of these sera. IgE antibodies to Acid P, HYAL, or melittin were present in 60%, 51%, and 31% of sera, respectively, and accounted for the highest level of binding in 17%, 17%, and 6% of these. Only 6% of sera were positive for whole venom but negative for the isolated antigens. A low level of IgE antibody was found to peptide 401 in 6% of sera. No IgE antibodies were found to apamin. While confirming the central role played by PLA2 in bee sting allergy, these results show that other venom components are also important in some patients.

IMMUNOLOGICAL FEATURES OF WEGENER'S GRANULOMATOSIS

Abstract A number of immunological markers were studied in ten patients with Wegeners granulomatosis or non-healing midline granuloma. The concentrations of serum IgA and C3 were increased. Autoantibodies to smooth muscle were noted in four cases. Cell-mediated immune studies showed a lack of correlation between an intact macrophage migration inhibition function and impaired skin delayed hypersensitivity and lymphocyte transformation to a number of antigens. It is suggested that Wegeners granulomatosis may be associated with a partial, cell-mediated immunodeficiency.

Skin responses to intradermal histamine and leukotrienes C4, D4, and E4 in patients with chronic idiopathic urticaria and in normal subjects

Mast cell inflammatory mediators, such as histamine, and newly formed compounds, such as the leukotrienes, cause wheal and flare when they are injected intradermally into normal subjects and may therefore play a role in the formation of urticaria. The effects of intradermal injections (50 microliters) of six different concentrations of histamine (range, 3.3 x 10(-4) to 3.3 x 10(-9) mol/L) and the leukotrienes C4, D4, and E4 (range, 2 x 10(-4) to 2 x 10(-9) mol/L) have been compared in 10 normal subjects and in 10 patients with chronic idiopathic urticaria. Wheal-and-flare sizes were measured at timed intervals up to 4 hours, and area under the curve for each response over time was calculated. There were no significant differences in leukotriene-induced responses between groups. Maximum sizes of histamine-induced wheal and flare were similar in each group of subjects. There were, however, significant increases in mean areas under the response curve of histamine wheal and flare in the patients with urticaria (wheal, p less than 0.001; flare, p less than 0.001; analysis of variance). These findings demonstrate a prolongation of skin responses to histamine in patients with urticaria and suggest an impaired clearance of histamine (or other vasoactive agents released by histamine) from the skin of these patients.

Allergy to castor bean:I. Its relationship to sensitization to common inhalant allergens (atopy)

The IgE response to castor bean (Ricinus communis) was studied in 96 castor bean-allergic patients from Marseilles, France. All had positive skin tests to castor bean. The IgE response to grass, cat, dust mite, olive, and Parietaria was also measured, and a positive RAST to one or more of these allergens was taken to indicate atopic status. Castor bean-specific IgE antibodies, measured by RAST, were found in 87 (91%) of the castor bean-allergic patients, in two of 13 atopic Marseilles residents living close to the castor bean mills, in three of 42 allergic subjects who had no known contact with castor bean, and in none of a control group of 111 Marseilles blood donors. Very high levels of castor bean-specific IgE (maximum class 4 readings on the Phadebas RAST score) were found in 54 (56%) of the castor bean-allergic patients, but the level of IgE antibody to castor bean was not significantly different in atopic and nonatopic subjects. The frequency of a positive serological test (RAST) for atopy in castor bean-allergic subjects (32%) was very similar to that found in the local population (36%). These data indicate that castor bean is an extremely potent sensitizer for both atopic and nonatopic individuals. The magnitude of the specific IgE antibody response is not related to the atopic status of the patient and may be a function of the physiochemical characteristics of the allergen itself.

PROSTAGLANDIN-SYNTHESIS INHIBITORS IN PROPHYLAXIS OF FOOD INTOLERANCE

Prophylactic doses of aspirin, indomethacin, or ibuprofen prevented symptoms of food intolerance in five out of six patients who on several occasions had had acute gastrointestinal symptoms after the ingestion of specific foodstuffs. Blood and stool prostaglandin E2 and F2alpha concentrations during unprotected challenge were consistent with the idea that these symptoms were mediated through prostaglandin release. Prostaglandin-synthetase inhibitors may benefit some patients with specific food intolerance who are unable or unwilling to avoid the offending food.

The IgE and IgG subclass antibody response to foods in babies during the first year of life and their relationship to feeding regimen and the development of food allergy

This follow-up study of 191 babies investigated the development of food allergy in an unselected population and its relationship to total and antigen-specific IgE and IgG subclass levels. Sensitization to egg, as indicated by a positive skin test or RAST, was found in 5% of 1-year-old babies, but none of the babies in this series fulfilled the clinical criteria for immediate-type milk allergy. For both bovine casein (CAS) and egg albumin, the IgG response was largely restricted to IgG1 in contrast to the predominant IgG4 response to these antigens that is found in adults. The level of IgG4, but not IgG1, antibody to CAS and ovalbumin (OV) was lower in some of the babies compared with that of their mothers (N = 166; p less than 0.05, Students paired t test). However, there was no difference in the total serum IgG subclass levels between mothers and babies. These results demonstrate that, in the population of babies studied, (1) type I hypersensitivity to egg occurred in 5% of 1-year-old babies, (2) the predominant IgG subclass of antibodies to CAS and OV in babies is IgG1, and (3) in the 22% of babies, there was substantially (greater than 1000-fold) less IgG4 antibody to CAS and OV than in their mothers, suggesting specific exclusion of some IgG4 antibodies.