CD-sens: a biological measure of immunological changes stimulated by ASIT.

BACKGROUND: Allergen-specific immunotherapy (ASIT) in allergic rhinitis and asthma is the only treatment that effects the long-term development of these diseases. Basophil allergen threshold sensitivity, CD-sens, which is a valuable complement to resource-demanding clinical challenge tests, was used to monitor the initiation of ASIT induced allergen 'blocking activity'. METHODS: Patients IgE-sensitized to timothy (n = 14) or birch (n = 19) pollen were started on conventional (8-16 weeks) or ultra rush ASIT, respectively, and followed by measurements of CD-sens, allergen binding activity (ABA) and serum IgG4- and IgE-antibody concentrations. RESULTS: CD-sens decreased during the early phase of ASIT-treatment. In parallel, ABA increased and correlated significantly with the increasing levels of IgG4 antibody concentrations. High dosages of allergen were more effective while mode of dosing up did not seem to matter. No change was seen in basophil reactivity. CONCLUSION: CD-sens and ABA, in contrast to basophil reactivity, seem to be promising tools to monitor protective immune responses initiated by ASIT.

Omalizumab and the immune system: an overview of preclinical and clinical data.

OBJECTIVE: This review discusses the role of immunoglobulin (Ig)E in allergic disease, inhibition of IgE with omalizumab, and the consequences of IgE inhibition (both clinically and in terms of the effect on the immune system). DATA SOURCES: Relevant publications obtained from a literature review. STUDY SELECTION: Relevant publications on IgE, allergic disease, and anti-IgE were critically evaluated. RESULTS: IgE plays a key role in allergic diseases such as allergic asthma and allergic rhinitis. Its role in healthy individuals is less well defined. Treatment of allergic asthma and rhinitis with omalizumab, a humanized monoclonal anti-IgE antibody, causes a marked reduction in circulating free IgE levels. This has been shown to reduce symptoms and decrease the need for other medication in patients with these allergic diseases. Anti-IgE treatment with omalizumab did not cause any of the complications that might, in theory, be expected to result from reduction in circulating free IgE, such as adverse effects upon the immune system or other body systems. CONCLUSIONS: The limited clinical data currently available suggest that this novel method of treatment for allergic asthma and rhinitis seems to be both effective and well tolerated in clinical use.

Increasing prevalence of asthma over 12 years among dairy farmers on Gotland, Sweden: storage mites remain dominant allergens.

BACKGROUND: Earlier studies from several countries have shown that IgE-mediated allergy in rural populations is of considerable importance and that storage mites are dominant allergens. OBJECTIVE: In an epidemiological follow-up study among farmers on the island of Gotland, Sweden in 1996 we wished to investigate the prevalence of respiratory allergy and to find out whether storage mites are still important allergens in a farming environment. METHODS: A questionnaire concerning airway symptoms, social and working conditions and smoking habits was distributed to all Gotland farmers aged 15-65 years and was completed by 1577 (86.7%), of whom 1015 were dairy farmers. Based on the answers, 500 dairy farmers were invited to undergo a medical examination which included a skin-prick test (SPT) and blood sampling for RAST analyses. Prevalence figures (symptoms, RAST and SPT) given for the whole population (n = 1015) were based on the investigation of the 461 farmers who took part in the examination. RESULTS: Immediate onset hypersensitivity was present in 41.7% of the 1015 farmers studied, which is almost the same figure as in 1984 (40.0%). The prevalence of asthma had increased significantly during the previous 12 years (5.3% vs 9.8%), as had asthma in combination with rhinoconjunctivitis (3.7% vs 7.0%). Rhinoconjunctivitis, on the other hand, had not changed significantly (36.5% vs 33.1%) and remained one of the most common symptoms. The prevalence of storage mite allergy in the farming population in 1996 was 6.5% and constituted an important cause of allergic symptoms. CONCLUSION: Over 12 years, Gotland dairy farmers have developed significantly more respiratory symptoms from the lower airways, although the proportion with atopy is unchanged. Storage mites are still dominant allergens for developing allergic disease.

The degree of natural allergen exposure modifies eosinophil activity markers in the circulation of patients with mild asthma.

We have previously found that CD9, CD11b, and intracellular ECP (EG2) may be used as activity markers for eosinophils in vitro. The main object of the present study was to determine whether these markers can reflect eosinophil activation in vivo in relation to allergen exposure. for this purpose, six patients with a history of allergic rhinitis and occasional asthma symptoms during the pollen season participated. Blood donors served as controls. Peripheral blood eosinophils were analyzed according to the FOG method and flow cytometry, before and during one birch pollen season with high pollen load (HPL) and one with low pollen load (LPL). The CD9 expression on peripheral eosinophils from the patients was significantly increased both before (P < 0.05) and during (P < 0.01) HPL season, and CD11b expression solely during HPL season (P = 0.01) as compared to controls. The intracellular expression of the EG2 epitope was increased before (P < 0.01) and during (P < 0.05) HPL season, and increased significantly (P < 0.05) during season as compared to before. No changes were observed before and during LPL season. The proportion of eosinophils was increased both before (P < 0.05) and during (P < 0.001) the HPL season as compared to controls. The markers CD9, EG2, and, to a lesser extent, CD11b seem to detect activated eosinophils in the circulation, whereas EG2 may also reflect increased antigen exposure during season.

Celery allergy associated with birch and mugwort pollinosis.

Skin prick tests (SPT) with various celery, carrot and potato preparations (raw, cooked, cooking water of each vegetable and allergen extracts) as well as specific IgE determinations by RAST to celery mix, celeriac (or root celery), stick celery and heated celery extracts were performed in 70 patients with positive prick or intracutaneous tests to birch and/or mugwort pollens and celery (extract and/or raw). 94% of the patients showed positive prick tests to raw celeriac, 36% to cooked celeriac and 8/13 to cooking water. Celery-birch positive patients (n = 13) showed negative or low RASTs to heated celery extracts and to stick celery. By contrast, in the celery-mugwort sensitive patients (n = 6) the celery RASTs with heated celery extracts remained clearly positive and high RAST values to stick celery could be found. Celery-birch-mugwort-association (n = 22) favoured more positive results with relatively high values of RAST to celeriac. The results of homologous and heterologous RAST inhibition experiments with birch, mugwort, unheated and heated celery (100 degrees C) carried out in nine celery-RAST positive sera are also discussed.

Characterization of allergenic components in sap extract from the weeping fig (Ficus benjamina).

The allergen composition of crude extract from sap (latex) of the weeping fig (Ficus benjamina) was investigated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and immunoblotting. The allergenic components were detected by sera from 11 occupationally exposed plant keepers, of whom 7 were non-atopic, and from 9 non-occupationally exposed atopic patients with a positive radio-allergosorbent test to weeping fig. The allergen-antibody complexes were visualized by rabbit anti-IgE and beta-galactosidase-labelled sheep anti-rabbit IgG, using a chromogenic insoluble substrate. A total of 11 allergenic components were identified. Three of them were found to be major allergenic components, identified by more than 50% of the investigated sera. These 3 IgE-binding components had molecular weights of approximately 29,000, 28,000 and 25,000 daltons, respectively. The major allergenic components were denatured by heat in the temperature range of 60-90 degrees C.

Effects of maternal diet during late pregnancy and lactation on the development of atopic diseases in infants up to 18 months of age--in-vivo results.

One hundred and sixty-two women with respiratory allergy to animal danders and/or pollens were randomly allocated to a diet consisting of either a very low ingestion of hens' egg and cows' milk or a daily ingestion of one hens' egg and about 11 of cows' milk during the last 3 months of pregnancy. One hundred and sixty-three infants were followed prospectively up to 18 months of age when the cumulated incidence of atopic disease in each child was evaluated blindly. No significant differences in the distribution of atopic disease were found among the infants in relation to the maternal diet during late pregnancy. The numbers of skin-prick tests positive to ovalbumin, ovomucoid, beta-lactoglobulin and cows' milk were likewise not influenced by differences in the maternal diet during late pregnancy. Genetic factors rather than maternal diet during the perinatal period probably have a greater effect on the incidence of atopic diseases during early infancy.

Demonstration of human, rye grass pollen extract-specific, helper and suppressor stimulating activity of modified allergens by effects on in vitro hapten-specific antibody production.

An in vivo system is described in which penicilloyl antibody was produced from peripheral leucocytes of a grass pollen-sensitive patient who had received penicillin therapy, by challenge of the cells with penicilloyl-grass pollen extract conjugate. Incubation of these leucocytes with a number of modified preparations of grass pollen extract with various T-cell-stimulating properties was shown to affect penicilloyl antibody production. Both chymotryptically fragmented rye grass pollen extract and a conjugate of f met-leu-phe and rye grass pollen extract enhanced penicilloyl-specific antibody similarly to the enhancement induced by unmodified extract, though at high concentration some suppression was seen. A conjugate of polysarcosine and rye grass pollen extract, previously shown to cause antibody suppression in mice, was similarly suppressive for penicilloyl-specific antibody. The system therefore shows potential for the evaluation of the effects of modified allergen treatment on antibody levels via T-cell mechanisms.

Predominance of mite allergy over allergy to pollens and animal danders in a farming population.

The prevalence of IgE-mediated hypersensitivity to respiratory allergens, including Lepidoglyphus destructor (a storage mite) and Dermatophagoides pteronyssinus, was studied in a rural population of Gotland, a Swedish island in the Baltic Sea. A sample of 440 farmers underwent examination, comprising skin-prick tests (animal danders, pollens, moulds, house dust mite and wheat) and blood sampling for radio-allergosorbent tests (RAST) (birch, Timothy grass, dog, D. pteronyssinus, Cladosporium and L. destructor). The highest prevalence of positive skin-prick tests was noted for D. pteronyssinus (6.0%). Low prevalences of positive skin-prick tests, 0.7-2.7%, were found for pollens, animal danders and moulds. Among the tested allergens, D. pteronyssinus and L. destructor yielded the highest prevalences of positive RAST results, namely 5.2 and 6.8%, respectively. Most farmers with allergy to pollens and animal danders had symptoms both from the upper and lower airways and from the eyes. Among farmers with both asthma and rhinoconjunctivitis, the prevalence of positive RAST results for L. destructor and D. pteronyssinus were simiar. The present study clearly demonstrates that mites are by far the most important allergens in the farming population on Gotland, whereas otherwise common allergens such as pollen and animal danders are clearly less significant.

Timothy-specific IgG antibody levels vary with the pollen seasons.

Serum samples were collected from eight grass pollen hypersensitive children during a 4-year period. The sera were assayed for contents of timothy-specific IgE antibodies by RAST. Timothy-specific IgG and IgA antibodies were quantified by a refined ELISA in which covalent binding of the antigen to the polystyrene solid phase had been performed. IgG antibodies were also assayed by a Sepharose-protein-A technique with radiolabelled timothy allergens as the antigen. It was possible to register clearcut seasonal variations with postseasonally boosted antibody levels not only of timothy-specific IgE but also of IgG antibody. Both IgG1 and IgG4 antibodies specific for timothy showed seasonal variations of a similar degree. It was not possible to register seasonal variations of the same magnitude of timothy-specific IgA antibodies.

Clinical and immunological effects of oral immunotherapy with a standardized birch pollen extract.

Oral immunotherapy (IT) was evaluated in a pilot study in two centres in children aged 8-15 years with allergic rhinoconjunctivitis. High doses (up to 20 X 10(6) BU monthly) of a defined freeze-dried birch pollen extract administered in enteric-coated gelatine capsules were given either daily for seven consecutive days every month or once weekly. Symptom scores, as assessed by sneezing, dripping and blockage of the nose, and redness, itching and swelling of the eyes, were significantly lower in treated patients compared to untreated, or placebo treated controls after 3 to 5 months of therapy. In all the 16 treated, but only in three of eight untreated patients, the scores were lower during the pollen season 1982 than during the pollen season preceding the treatment period, despite comparable pollen counts during the two seasons. One year after beginning treatment the reactivity in conjunctival provocation tests was decreased about 10-fold (P less than 0.001) in the patients receiving more than 2 X 10(5) BU monthly compared to about two-fold in patients receiving lower doses, or placebo. Increased levels of IgE antibodies directed against birch pollen were recorded in the serum and saliva of most patients after 3-4 months of active IT. In contrast, IgG antibody responses were poor in most of the patients. Side effects, particularly from the gastrointestinal tract, appeared in all treated children. In one of them a systemic reaction occurred during IT. The study indicates that properly performed oral IT with a potent birch allergen extract in enteric-coated capsules may be effective.

IgE-mediated anaphylaxis to mustard.

A young woman had recurrent urticaria and angioneurotic edema following ingestion of mustard and mayonnaise. IgE-mediated allergy to mustard seeds and seeds of botanically related plants was confirmed by RAST.

Diagnostic tests in allergy to green coffee.

Twenty-two coffee roastery workers with work-related symptoms of various degree from the eyes, nose or bronchi were tested with partly purified water-soluble extract from dust of green coffee beans (GCB). Eighteen persons had a positive prick test, eight a positive bronchial provocation test and seven a positive nasal provocation test. Fourteen had a positive methacholine test, indicating unspecific bronchial hyperreactivity. Specific IgE antibodies to GCB extract were found in sera of 11 workers and to castor bean (CB) extract in 16. The workers measured their lung function with an air flow meter, three times a day for 1 week, and the values were lower in the second half of the week for the workers with IgE antibodies to GCB, but not for the others. It is concluded that the case history, prick test, RAST, and simple lung function tests for one or a few weeks are the best tools when investigating occupational allergy. When the allergen is unknown, but the occurrence of an IgE-mediated allergy is suspected, serial lung function measurements and determinations of total serum IgE, in addition to taking a careful case history, are valuable methods with which to start the investigation.

Coffee worker's allergy.

Workers in the coffee industry were investigated. Study I comprised 50 selected cases of whom 25 had work-related symptoms and 25 had not. Prick tests and RAST investigations with different factory dust extracts were performed. Study II was a cross-sectional study comprising 129 workers who were prick-tested with one factory dust extract and with castor bean (CB). More than 40% described occupationally related asthma, rhinitis, conjunctivitis or pruritus, and in about half of these cases sensitization with one or two allergens was found. One allergen comes from coffee beans and is found in the factory dust, mainly where the raw coffee is handled. This allergen is destroyed in the roasting process. The other allergen is identical with the allergen from castor bean and its presumed to enter the plant via the sacks. Predisposing factors to developing sensitization were atopic status, degree and length of exposure, and smoking habits.

Clinical studies of a purified timothy pollen extract: desensitization therapy with a purified timothy pollen preparation compared to a crude timothy pollen extract. II. Results of the tests in vitro and their relation to symptoms and tests in vivo.

Perennial desensitization therapy was given during a period of 3.5 years to 40 children allergic to grass pollen allergens. 20 patients were treated with a crude and another 20 with a purified timothy pollen extract. 8 children served as untreated controls. The concentration of total and specific IgE in the treated groups covaried with those in the control group. Neither a suppression of the seasonal booster effect nor a suppression of IgE synthesis attributable to the treatment was found. The rise of timothy-specific "blocking' IgG antibodies was more pronounced in the group treated with the purified extract than in the group treated with the crude extract. A significant difference was found only after 3.5 years of treatment. The amplitude of rise of IgG antibodies correlated significantly with the effect of the treatment as judged by repeated conjunctival titration test. The results suggest that a good IgG response is an indication of successful therapy and that a better IgG response may be achieved with purified allergen extracts.

Use of glutaraldehyde-modified timothy grass pollen extract in nasal hyposensitisation treatment of hay fever.

12 patients suffering from grass pollen hay fever were treated for 14 weeks pre- and co-seasonally by intranasal self-administration of an aqueous solution of a glutaraldehyde-treated timothy grass pollen allergen. These patients had a statistically significant decrease in nasal symptom scores during the grass pollen peak period and in nasal challenge end-point titre after the season compared to placebo-treated patients. No significant effect was seen on the eye symptoms. 1 patient withdrew from the trial as a consequence of too strong local nasal reactions during treatment. Most other patients treated with active material reported mild local reactions during the first minutes after administration of the nasal spray. In the actively treated group a significant increase in serum and nasal secretion of grass pollen specific IgE, IgG and IgA antibodies was obtained during the treatment. In contrast, in the placebo group a significant increase in IgE antibody levels in serum and secretion occurred during the pollen season. The reduction in symptoms and increase in antibody production together with the simplicity of the procedure makes this approach to immunotherapy attractive.

Immunological studies in vitro and in vivo of children with pollenosis given immunotherapy with an aqueous and a glutaraldehyde-treated tyrosine-absorbed grass pollen extract.

Ten patients treated with an aqueous Timothy grass pollen extracts and given monthly maintenance doses were compared to ten patients given a glutaraldehyde-treated tyrosine-adsorbed grass pollen extract as five weekly injections pre-seasonally. There were four non-treated controls. Both treated groups showed equivalent increases of total IgE, Timothy-specific IgE, and IgG, but the concentrations of Timothy-specific IgG antibodies were sustained only in the patients receiving maintenance therapy. An increase of IgE and RAST titres during the pollen season were obtained in all three groups. No consistent changes were seen in the results of leucocyte histamine release tests and naso-conjunctival provocation tests from spring to autumn. A Sepharo-protein A technique was used for the estimation of Timothy-specific IgG antibodies. The results obtained with this technique correlated excellently with those of the Farr technique and a double-antibody technique.

In vitro cross-allergenicity of major aeroallergenic pollens by the radioallergosorbent technique.

Cross-reactivity between major classes of aeroallergenic pollens has been estimated by comparing the inhibitory effects of selected allergens upon the reaginic activity of other native and non-native varieties, as measured by the radioallergosorbent technique (RAST). Common allergenic determinants were demonstrated in indigenous and nonindigenous ragween species. Although patterns of inhibitory capacity were less uniform among grass pollens, endemic species tended to have more common allergenic properties than nonendemic species. Tree pollens exhibited the greatest degree of heterogeneity, confirming the previous view that these pollens tend to be less cross-reactive. Concomitant skin test threshold studies utilizing the same groups of pollens were in general agreement with in vitro results. Because, threshold skin testing was affected by a number of uncontrollable variables, however, the current modification of RAST in estimating cross-allergenicity was more accurate and reliable than data based upon cutaneous tests. It was concluded that reagin neutralization by the RAST method is the best currently available method of assessing cross-allergenic properties of pollens.