Dust mite allergens and asthma: report of a second international workshop.
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Allergens↗
Biomedical subjects
R C Aalberse
Publications and source records attributed to R C Aalberse.
Variability of crossreactivity of IgE antibodies to group I and V allergens in eight grass pollen species.
Crossreactivity to Dactylis glomerata, Festuca rubra, Phleum pratense, Anthoxanthum odoratum, Secale cereale, Zea mays, and Phragmites communis of IgE antibodies against Lol p I or Lol p V was investigated by means of RAST-inhibition. Within a group of sera the degree of crossreactivity was demonstrated to be highly variable. Individual sera were not always equally crossreactive to all pollen species. A high degree of crossreactivity for Group I allergens did not necessarily implicate the same for Group V. Group I and Group V representatives were found to be present in all eight species. It was demonstrated that within this group of grass species significant quantitative and qualitative differences exist, with respect to Group I and Group V allergens. Species with a low phylogenetic affinity to Lolium perenne, like Zea mays and Phragmites communis showed a very low degree of reactivity, even when measured with the most crossreactive sera. A higher taxonomic relationship however, did not always implicate a closer antigenic resemblance. Antigenically both allergens from Zea mays are more similar to Lol p I and Lol p V, than the analogues in Secale cereale.
Allergens↗
'Horoscope effect' not only for seasonal but also for non-seasonal allergens.
We report on the relation between the month of birth and the chance of developing an IgE antibody response as found in a study sample of 150,000 subjects. Our results confirm that for the three seasonal allergens birch pollen, grass pollen and house dust mite, an increased relative risk was found for subjects born up to 3 months before the main season for that allergen in The Netherlands. For cat and dog allergy an increased relative risk was found from November to January, perhaps reflecting increased exposure to these pets during the winter. Surprisingly, however, also for egg white and cow's milk a clearly increased relative risk was found from November to January and a decreased relative risk in May. These data support the hypothesis of a 'sensitive' period in the first months of life during which allergen exposure is more likely to prime for an allergy later in life. The results with the non-seasonal allergens suggest that another seasonal factor exists which early in life assists (or prevents) priming by allergen.
Allergens↗
The potent IgG4-inducing antigen in banana is a mannose-binding lectin, BanLec-I.
IgG4 antibodies to banana were found to occur far more frequently than expected. The most important antigen involved proved to be a lectin, BanLec-I. Because of the lectin nature of the antigen, it was important to establish the antibody nature of the lectin-IgG4 interaction and to exclude an interaction between the sugar-binding site of the lectin and glycosidic chains on IgG4. Three arguments in support of immune binding are: (1) the binding of BanLec-I to IgG4 is mannoside resistant, whereas the binding to all other glycoproteins tested is mannoside inhibitable; (2) only a minor fraction of the IgG4 in serum and none of five IgG4 myelomas tested was bound, and (3) the lectin binds to the Fab fragment of the IgG4 molecule. A curious finding was that in the presence of high-molecular-weight glycoproteins the interaction between IgG4 and BanLec-I was enhanced by alpha-methyl mannoside. The probable explanation of this phenomenon is that complexes of the lectin with high-molecular-weight glycoproteins by sterical interference inhibit the interaction with human IgG4 antibodies (or with rabbit antibodies to the lectin). This inhibition is prevented in the presence of alpha-methyl mannoside. These results support the earlier suggestion that some lectins are particularly prone to induce an immune response upon oral feeding. This banana lectin might be a potentially useful carrier protein for oral antihapten immunization in humans.
Antigens↗
Profilin is a cross-reactive allergen in pollen and vegetable foods.
Sera with IgE antibodies against grass pollen often contain IgE against vegetable foods. We investigated the role of the ubiquitous protein profilin in this cross-reactivity. Profilin was purified from Lolium perenne grass pollen by means of affinity purification with Sepharose-coupled poly(L-proline). This solid phase was also used as capturing agent for profilin from pollen and food extracts for application in a radioallergosorbent test. It was shown that profilin is an allergen in grass pollen and in a wide range of vegetable foods, like potato and celery. Within a grass-pollen-sensitive population, patients with IgE to vegetable foods have a high incidence of antibodies against profilin. IgE antibodies against grass pollen profilin were shown to be cross-reactive with respect to vegetable foods.
Allergens↗
Structure of the major cat allergen Fel d I in different allergen sources: an immunoblotting analysis with monoclonal antibodies against denatured Fel d I and human IgE.
In this paper we show the reactivity of monoclonal antibodies (mAbs) and human IgE with Fel d I from different allergen sources in reduced SDS-PAGE immunoblots. By SDS-PAGE analysis of affinity-purified 125I-Fel d I, a 14- to 20-kD band was found, which dissociated under reducing conditions into a 4- to 5-kD chain (chain 1) and a 11- to 15-kD chain (chain 2). In initial immunoblotting experiments with mAbs against Fel d I however, only chain 1 was detected, while the mAbs lost activity upon reduction of Fel d I. Therefore mAbs were raised against reduced and alkylated Fel d I. Two of the four mAbs to 'denatured' Fel d I that were obtained did react with chain 2 on an immunoblot under reducing conditions; the other two reacted with chain 1. The mAbs did not react with native Fel d I. With these mAbs and human IgE, differences between allergen source materials in blot patterns of Fel d I were detected. A variable molecular weight for the protein stained with mAb antichain 2 was found, and occasionally the presence of a 12-kD band stained with mAb antichain 1. Human IgE strongly bound to chain 1 of Fel d I, while only 2 out of 6 sera gave a strong reaction with chain 2. The additional 12-kD band was also recognized by human IgE. In a competitive radioimmunoassay with mAb antichain 1, differences in levels of 'denatured' Fel d I between commercial extracts were quantitated. In vitro 'denatured' Fel d I was generated under high pH conditions. The reactivity of human IgE with this 'denatured' Fel d I was demonstrated in indirect RAST experiments with mAb antichain 1. We conclude that mAb antichain 1 recognizes a form of Fel d I that is not detected by mAb antinative Fel d I, but does react with human IgE.
Allergens↗
Newly generated IgE antibodies to Dermatophagoides pteronyssinus in children are directed against components distinct from Der p I and Der p II.
The specificity of newly generated IgE antibodies (Abs) to the house dust mite, Dermatophagoides pteronyssinus, in longitudinal serum samples from 18 young children with an increased risk for IgE-mediated allergy was studied. The first IgE Ab response to house dust mite was detected early in life (mean age, 32 months; range, 11 to 60 months). For 83% of the children, more than half of the newly generated IgE Ab response to house dust mite was directed against components distinct from the major allergens, Der p I (Pl) and Der p II (DpX). These results suggest that the early IgE Ab response to house dust mite is induced by components distinct from the major allergens, Der p I and Der p II.
Allergens↗
Affinity purification of a major and a minor allergen from dog extract: serologic activity of affinity-purified Can f I and of Can f I-depleted extract.
Most dog-allergic patients react to a major 25 kd component on sodium dodecyl sulfate blots, Can f I (Ag 13). We initially raised monoclonal antibodies (Cf-3 and Cf-2) reactive with IgE-binding components distinct from Can f I. After a slight modification, we immunized other strains of mice and produced monoclonal antibodies coded Cf-1a and Cf-1b reactive with Can f 1. We affinity purified the allergens, Can f I and "dog allergen 2" with Cf-1a and Cf-2 ascites, respectively, and house dust-rich dog dander. Comparison of purified Can f I with dog saliva in RAST demonstrated that Can f I is a potent allergen for most dog-allergic patients (average response, 70%). After depletion of dog saliva of Can f I, a slightly lower contribution for Can f I was found, but the overall results supported the conclusion that Can f I is a major allergen in dog saliva. Comparison of purified dog allergen 2 with dog dander in RAST demonstrated that dog allergen 2 is less important for dog-allergic patients (average response, 23%). We radiolabeled the purified allergens and developed assays to measure Can f I and dog allergen 2 in allergen extracts and dust samples. Dog saliva was a strong allergen source, dog urine and feces contained very little of the allergens, and both allergens were found to a variable degree in the nine dog breeds tested.
Allergens↗
Epitope mapping of the Dermatophagoides pteronyssinus house dust mite major allergen Der p II using overlapping synthetic peptides.
Fourteen synthetic peptides of 15 amino acid residues length, overlapping by five residues and spanning the entire sequence of the major allergen Der p II from the house dust mite Dermatophagoides pteronyssinus were synthesized. These peptides were coupled to CNBr-activated Sepharose-4B and used as solid-phase antigens in epitope mapping studies using human IgE antisera. These antibodies bound predominantly to the peptide comprising residues 65-78, the binding of which was inhibited by native Der p II. In addition these antisera bound, to a lesser extent, to the peptide that comprised residues 1-15, which binding was not inhibited by native Der p II. Thus, we found one sequential epitope for a number of IgE sera.
Allergens↗
Relationship between IgG1 and IgG4 antibodies to foods and the development of IgE antibodies to inhalant allergens. I. Establishment of a scoring system for the overall food responsiveness and its application to 213 unselected children.
To obtain reference levels for subsequent investigations, we analysed the IgG1 and IgG4 antibody levels to common foods in the sera of 213 unselected children (age 3 months to 14 years). The children were clustered into five age groups and tested on a broad screening panel of common foods. We used the IgG1 and IgG4 RAST with Sepharose-coupled antigens: cows' milk, hens' egg white, banana, legumes (a mixture of soybean and peanut), grains (a mixture of wheat and rice), potato, orange and pork. In all age groups and all antigens, a considerable variability in the antibody response was found. As for some assays more than half of the sera were negative or borderline, statistics based on interval or ordinal scaling were considered inappropriate and we resorted to nominal classification. We decided to use, for each of the assays, the 75-percentile of the age group as a cut-off level. Each antibody titre was thus converted into positive (more than the 75-percentile of that age group) or negative; the number of positive tests was used as the score. This resulted in a sigma G1-score and a sigma G4 score (summed scores for IgG1 and IgG4 antibodies, respectively). The results of the present study indicate that children with a high response to one food tend to have elevated responses to other non-related foods, possibly explained by a defective mucosal barrier and/or a hyperactive immune system. This suggests that a high-food responder phenotype may exist.
Adolescent↗
Relationship between IgG1 and IgG4 antibodies to foods and the development of IgE antibodies to inhalant allergens. II. Increased levels of IgG antibodies to foods in children who subsequently develop IgE antibodies to inhalant allergens.
In the present investigation we have tested the hypothesis that children with a high IgG antibody response to foods have an increased risk of developing IgE antibodies to inhalant allergens. Sera from 106 children with an increased risk of developing IgE-mediated allergy were analysed. During the follow-up, in 54 of these children IgE antibodies to inhalant allergens appeared. A positive/negative IgG1 and IgG4 anti-food score was determined as described previously: sera from age-clustered unselected children were tested for the levels of IgG1 and IgG4 antibodies to common foods. For each IgG RAST and each age group, the 75-percentile was chosen as cut-off value. Each antibody level was thus converted into a positive (higher than the 75-percentile of the age group) or negative value. The number of positive tests was used as the score. High-risk children with a high IgG1 anti-food score more often developed inhalant-specific IgE antibodies than high-risk children with low IgG1 titres: 50% of the children with a high IgG1 anti-food score developed IgE antibodies to grass pollen. Fifty per cent of the children with a high and 14% of the children with a low IgG1 anti-food score developed IgE antibodies to cat dander. For the prediction of the development of IgE anti-mite (house dust mite), the IgG4 anti-food scores appeared less useful than the IgG1 anti-food scores; 46% of the IgG4 high responders versus 22% of the IgG4 low responders acquired IgE anti-mite, whereas for IgG1 these percentages were 73 and 19, respectively.
Allergens↗
The IgE response and atopy.
The relationship between atopy and immunoglobulin E (IgE) is discussed. The following conclusions/hypotheses are reached: 1. IgE is typical of, but not unique for atopy. 2. IgE is specific for atopy under conditions of marginal antigen presentation. 3. Under normal antigen stimulation conditions, i.e. conditions which lead to the formation of antibodies but not usually to that of IgE antibodies, the IgE-route of B-cell activation/differentiation is blocked, perhaps by interference with the biological activity of CD23 by IgE. 4. Under "strong" antigen stimulation the IgE blockade is circumvented, presumably via the production of excessive amounts of interleukin-4 (IL-4). 5. Cross-reactive priming in the gut might enhance the induction of IgE antibodies to inhalant allergens, according to the principle "IgE breeds IgE".
Antibody Specificity↗
The role of IgG in immediate-type hypersensitivity.
Two opposed modes of action have been attributed to immunoglobulin G (IgG) in immediate-type allergy. On the one hand, a small fraction of IgG may have anaphylactic properties. On the other hand, IgG antibodies induced by hyposensitization therapy are considered to act as allergen blocking antibodies. The IgG4 isotype is the major antibody in the immune response induced by hyposensitization therapy and is presumably the only IgG subclass with homocytotropic properties. Immunochemical characteristics of IgG4, such as functional monovalency and inability to activate the complement system, underline the special place of this isotype in the humoral immune response. Detection of IgG4 antibodies in serum has a very limited use in allergy diagnosis. IgG4 antibodies do not appear to have anaphylactic properties, in spite of the homocytotropic activity suggested by some in vitro experiments. However, the assay may be of importance for measuring immune responses in occupational exposure to antigenic substances and in monitoring hyposensitization therapy.
Anaphylaxis↗
Isolation and characterization of BanLec-I, a mannoside-binding lectin from Musa paradisiac (banana).
A lectin (BanLec-I) from banana (Musa paradisiac) with a binding specificity for oligomannosidic glycans of size classes higher than (Man)6GlcNAc was isolated and purified by affinity chromatography on a Sephadex G-75 column. It did not agglutinate untreated human or sheep erythrocytes, but it did agglutinate rabbit erythrocytes. BanLec-I stimulated T-cell proliferation. On size-exclusion chromatography, BanLec-I has a molecular mass of approx. 27 kDa, and on SDS/PAGE the molecular mass is approx. 13 kDa. The isoelectric point is 7.2-7.5. BanLec-I was found to be very effective as a probe in detecting glycoproteins, e.g. on nitrocellulose blots.
Animals↗
Evidence for a Fel d I-like molecule in the "big cats" (Felidae species).
In this study, we investigated the cross-reactivity pattern of IgE and IgG4 antibodies to the major feline allergen, Fel d I. We studied the IgE and IgG4 response of 11 cat-allergic patients against Fel d I-like structures in eight members of the Felidae family: ocelot, puma, serval, siberian tiger, lion, jaguar, snow leopard, and caracal. Hair from these "big cats" was collected, extracted, and used in a RAST system and histamine-release test. By means of a RAST-inhibition assay with affinity-purified Fel d I from cat dander, it was established that, in the Felidae species, a Fel d I equivalent is present that reacts with IgE and IgG4 antibodies. We found that all patients had cross-reacting IgE antibodies to seven of the Felidae tested; no IgE antibodies reactive with the caracal were found. Eight of 10 patients with IgG4 antibodies directed to cat dander also had IgG4 antibodies directed to several Felidae species, including the caracal. However, the correlation between the IgE and the IgG4 antibody specificity was low, indicating that, in the case of Fel d I IgE and IgG4, antibodies do not necessarily have the same specificity.
Adolescent↗
Presence of Felis domesticus allergen I in the cat's salivary and lacrimal glands.
Most of the IgE response in persons allergic to cats is directed against the cat allergen Fel d I (Felis domesticus allergen I). Although the presence of Fel d I in saliva has been demonstrated, the source of Fel d I is not completely known. We measured Fel d I concentrations in the cat's lacrimal and salivary glands and in the excretes lacrimal fluid, milk and saliva. The concentration of Fel d I, determined by a radioimmunoassay, in the lacrimal gland was 390-780 mU/g tissue and in the sublingual gland 610 mU/g tissue. In the parotid gland and especially the submandibular gland only low concentrations were found, respectively 70-210 and 40-50 mU/g tissue. In lacrimal fluid 6.8-14 U/ml Fel d I was detected, which is comparable to saliva, 4.2-7.0 U/ml, whereas in cat's milk only 0.33 U/ml Fel d I was found. Immunohistochemical studies with monoclonal antibody directed against Fel d I (anti-Fel d I) showed the presence of Fel d I in the serous cells of the lacrimal gland. Thus, our results demonstrate that in particular the lacrimal gland might be a useful Fel d I source.
Allergens↗
Statistical analysis of IgE antibodies to the common inhalant allergens in 44,496 sera.
A statistical analysis of RAST screening of 44,496 sera, submitted in 1986 and 1987 for routine diagnostic allergic examination, was performed. The sera were tested on a fixed panel of allergens, regardless of the patient's history. The association of a positive RAST with age and month of birth was studied. It was concluded that among the inhalant allergens, house-dust mite was the most frequent sensitizer for all age groups, followed by grass pollen and cat dander. Sensitization to cat dander occurred twice as often as sensitization to dog dander. Among children less than 4 years of age, a different profile of sensitization was found, indoor allergens (mites, animal danders) being more important than outdoor allergens (pollen). Furthermore, we found that children born during December-February had a slightly but significantly greater chance of becoming sensitized to grass pollen compared with children born during September and November (P less than .05). Children born during July-September had a greater chance of becoming sensitized to house dust mite compared with children born during January-March (P less than .05). Finally, it was found that children born during October-December had a greater chance of becoming sensitized to dog dander compared with children born during March-May.
Administration, Inhalation↗
Cross-reactivity of IgE antibodies to caddis fly with arthropoda and mollusca.
We investigated the possibility that subjects with IgE antibodies to an inhalant insect allergen, such as caddis fly, might also have antibodies to cross-reacting carbohydrate determinants (CCDs). IgE antibodies to cross-reacting allergens in caddis flies, mussels, oysters, shrimps, crabs, honeybee, and yellow jacket venoms were determined by RAST, RAST inhibition, and immunoblot studies with sera from three different sources: (1) sera of patients with well-defined inhalant atopy to caddis fly, (2) sera with IgE anti-CCD antibodies from subjects without known exposure to caddis fly, and (3) hyperimmune antisera with IgG anti-CCD antibodies raised as a result of immunization of rabbits with grass-pollen extract, buckwheat glycoprotein, or with honeybee venom. Sera from groups 2 and 3 reacted with Sepharose-coupled caddis fly extract in a RAST-type assay and elicited virtually identical patterns on immunoblots of caddis fly extract separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, whereas the sera from group 1 atopic patients did not react with CCD-rich material. However, indications for other types of cross-reacting antibodies were detected. The IgE antibodies of one of the patients studied (who was allergic not only to caddis fly but also to shellfish) were found to detect a cross-reacting homologous protein in extracts of mussel, oyster, shrimp, crab, honeybee, and yellow jacket venom. Preliminary results suggest that this cross-reacting 13 kd protein, the most prominent caddis fly allergen, is an invertebrate hemoglobin (erythrocruorin)-like molecule. These studies suggest the possibility that patients sensitized by exposure to caddis fly antigens could develop allergic reactions during their first exposure to shellfish or to their first bee sting.
Adult↗