A revised nomenclature for allergy--reflexions of an old-timer.
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Allergy and Immunology↗
Biomedical subjects
A L de Weck
Publications and source records attributed to A L de Weck.
Atopic and nonatopic IgE-mediated allergy: a new interpretation of old facts?
Coined 80 years ago, the term 'atopy' to designate a group of diseases associated with IgE and a hereditary background has raised many discussions. In particular, it is difficult to consider as part of an atopic syndrome cases of IgE-mediated allergies to isolated allergens without evidence of a familial inheritance. The postulate expressed in this essay is that in humans we are essentially dealing with an atopic IgE-mediated allergy, which is the equivalent of a genetically determined high IgE response, and with a nonatopic IgE-mediated allergy, which is the equivalent of a low IgE response in mammals and rodents.
Allergens↗
Flow cytometric basophil activation test: a review.
Flow cytometry is a technique enabling the analysis of physical and biological characteristics of cells or other biological particles when labeled with antibodies coupled to fluorochromes or other dyes. The basophil activation test (BAT), also called flow-cytometric allergen stimulation test (FAST) [commercially available under the name of Flow CAST (Bühlmann Laboratories) or BASOTEST (Beckton-Dickinson)] is based on the in vitro allergen-induced specific activation of basophils. This assay rests on the demonstration of some membrane protein markers that appear after exposure to the allergen. This paper reviews some of the literature about the use of this technique in the investigation of immediate-type allergies to inhalant allergens, drugs, and foods, as well as our own experience with this diagnostic technique. Flow cytometry is a reliable method for the quantification of basophil activation after allergenic stimulus in vitro and in vivo. It also enables us to detect allergic and pseudoallergic reactions because of other mechanisms than allergen-specific IgE antibodies. Further clinical evaluation of this technique will allow validation and better establishment of its diagnostic value in allergy.
Adult↗
In vitro IgE but not IgG production of canine peripheral blood B cells is inhibited by CD40 ligation.
The aim of this study was to investigate in vitro IgE induction in peripheral canine B cells. CD21(+) B cells were purified from the peripheral blood of beagle dogs by positive selection via magnetic separation to a purity of >/=95%. Subsequently, proliferation, and IgG and IgE production of canine B cells were investigated after stimulation with human recombinant Interleukin-4 (hrIL-4) and human recombinant Interleukin-2 (hrIL-2) in the presence or absence of CD40L-CD8 fusion protein (CD40L) of mouse origin. We could demonstrate that canine B cells react on hrIL-2 alone by proliferation and IgG production but not by IgE secretion, whereas activation with hrIL-4 induced proliferation and mainly IgE production. Together, both cytokines synergistically increased B cell proliferation as well as IgG and IgE production. We could also show that mouse CD40L induces proliferation of dog B cells, which is further enhanced by addition of hrIL-4. Unexpectedly, CD40L led to a dramatic decrease in the IL-4 mediated IgE secretion (82% inhibition on an average). In contrast, IgG production was not affected significantly by CD40L. The same effects of CD40L were observed when B cells were stimulated by a combination of IL-2 and IL-4 and this inhibition could not be abrogated by increasing the amounts of IL-4. In summary, activation of canine B cells from peripheral blood by hrIL-4 in the presence or absence of hrIL-2 led to marked IgE production that is strongly and in a dose-dependent manner inhibited by CD40L. Stimulation of IgG production is not influenced by CD40L.
Animals↗
IgE-reactivity to major Japanese cedar (Cryptomeria japonica) pollen allergens (Cry j 1 and Cry j 2) by ELISA in dogs with atopic dermatitis.
The present study investigated IgE-reactivity to two major Japanese cedar (Cryptomeria japonica, C. japonica) pollen allergens (Cry j 1 and Cry j 2) in dogs with atopic dermatitis by use of a fluorometric ELISA. The serum samples from 27 dogs that showed IgE-sensitivity to crude C. japonica pollen allergen by ELISA were tested for specific IgE to the two major allergens. All 27 dogs had anti-Cry j 1 IgE, and 10 (37%) had anti-Cry j 2 IgE. Inhibition of binding of dog specific IgE to crude C. japonica pollen allergen was carried out by addition of Cry j 1. When serum samples containing anti-Cry j 1 IgE but no anti-Cry j 2 IgE were incubated with Cry j 1, specific IgE binding to crude C. japonica pollen allergen was almost abolished. These findings suggest that Cry j 1 is a major allergen in dogs.
Animals↗
IgE sensitivity and cross-reactivity to crude and purified mite allergens (Der f 1, Der f 2, Der p 1, Der p 2) in atopic dogs sensitive to Dermatophagoides mite allergens.
The present study investigates IgE-reactivity to crude and purified mite allergens by intradermal skin test (IDST), Immunodot method, and ELISA in atopic dogs sensitive to mite allergens, as well as the allergenic cross-reactivity between Dermatophgoides (D) farinae (DF) and D. pteronyssinus (DP) in dogs by IgE-ELISA inhibition. IDST and Immunodot method for crude mite allergens were performed for atopic dogs and 16 atopic dogs showed sensitivity to mite allergens. Of the 16 dogs, all dogs had anti-DF IgE and 11 had anti-DP IgE. We measured specific IgE to purified major allergens (Der f 1, Der f 2, Der p 1, Der p 2). Of the 16 atopic dogs, six had anti-Der f 1 IgE and seven had anti-Der f 2 IgE. Similarly, of the 16 dogs, six had anti-Der p 1 IgE and seven had anti-Der p 2 IgE. However, eight dogs had no specific IgE to these mite allergens. These dogs may be sensitive to other major mite allergens except Der 1 and Der 2. In the dogs that had both anti-DF and DP IgE, IgE binding to DF was greatly inhibited by DP, and reciprocal inhibition was observed. Based on these data, it appears that there is a strong cross-reactivity between DF and DP in dogs. Similarly, a cross-reactivity between DF and DP in purified allergens was also observed. IDST and Immunodot method are useful methods for the diagnosis of atopic diseases in dogs, and ELISA is a useful method for further investigation of IgE-reactivity for the allergens.
Allergens↗
Sulfidoleukotriene generation from peripheral blood leukocytes of horses affected with insect bite dermal hypersensitivity.
Sulfidoleukotrienes (sLT) generated in vitro after incubation of equine peripheral blood leukocytes (PBL) with different inducing agents were determined in 18 healthy and 16 insect bite dermal hypersensitivity (IDH)-affected horses. PBL from these 32 horses were stimulated with Concanavalin A, Parascaris equorum, Culicoides nubeculosus and Simulium extracts, and with a six-Grass mix. The cells of all but four horses generated sLT after incubation with Concanavalin A; these four horses did also not produce sLT with the other inducing agents. Of the 28 remaining horses (12 affected with IDH and 16 healthy), all but three generated sLT with the P. equorum extract. The six-Grass mix did not induce sLT production in any of the tested horses. sLT generation with Concanavalin A and Parascaris was statistically not different between IDH-affected and healthy horses. PBL of the diseased horses, however, produced significantly more sLT with the Culicoides (p < 0.01) and Simulium (p < 0.05) extracts than those of the healthy animals. Additionally, sLT generation with the Culicoides extract was measured at different times of the year in one IDH-affected animal and remained high even in winter, when the horse was asymptomatic. sLT and histamine release were determined in 10 horses in parallel. Positive correlations of 0.81 and 0.82 for Concanavalin A and Parascaris (p < 0.01 and p < 0.05, respectively), and of 0.95 and 0.94 for Culicoides and Simulium (p < 0.01) were found between sLT and histamine release. These results indicate that, alike in humans, sLT are released in vitro from equine basophils along with histamine in response to various stimuli and that immediate type hypersensitivity reactions to Culicoides and Simulium are often involved in the pathogenesis of IDH. Thus, sLT generation from equine basophils offers an in vitro diagnostic tool for IDH even in sensitised but asymptomatic horses.
Animals↗
Domain mapping and comparative binding features of eight dog IgE-specific reagents in ELISA, immunoblots, and immunohistochemistry.
Eight dog IgE-specific reagents including monoclonal and polyclonal antibodies (Ab) and a cross-reactive alpha chain of the human high affinity IgE receptor were mapped to recombinant fragments of the second (IgEf2) and third/fourth (IgEf3/4) domains of the dog IgE heavy chain. In ELISA, five out of eight reagents reacted to solid-phase bound IgEf2, of which two polyclonal Ab bound in addition to IgEf3/4. All Ab which recognized at least one recombinant IgE fragment, also bound to IgE in ELISA, immunoblots, and immunohistochemistry. In contrast, only one monoclonal Ab, that did not bind to the recombinant IgE fragments, reacted with immunoblots of serum and immunohistochemistry. The alpha chain could only be applied to ELISA with serum IgE. Furthermore, there was a wide range of heat-lability of binding reactions. Comparative analysis of available dog IgE-specific reagents enables more in-depth functional studies on IgE-mediated phenomena in dogs, and helps to further establish the dog as an animal model for allergy research.
Animals↗
Characterization of two dog IgE-specific antibodies elicited by different recombinant fragments of the epsilon chain in hens.
Two recombinant [His]6-tagged fragments of the canine immunoglobulin E (IgE) heavy chain (second domain: IgEf2 and third and fourth domains: IgEf3/4) were cloned, expressed in Escherichia coli (E. coli) as [His]6-tagged proteins, and affinity-purified over nickel-nitrilotriacetic acid columns. The recombinant proteins were used to immunize hens. The raised and affinity-purified chicken antibodies (Ab) isolated from egg yolk exhibited specific binding to the respective recombinant canine IgE fragment (IgEf) on immunoblots and displayed high titers against the IgEf in ELISA. Immunoblotting of canine serum separated by PAGE under native conditions with the IgEf2- and IgEf3/4-specific Ab resulted in staining of a protein of approximately 180 kilodaltons (kD). The IgEf3/4-specific Ab further recognized an 80 kD protein in IgEf3/4-specific Ab affinity-enriched dog serum separated under denaturing conditions. In an ELISA for the detection of antigen-specific IgE in dog serum, reduced binding of the IgEf-specific Ab was observed after heat treatment of the dog serum. The reactivity of both of the raised chicken Ab was only present in postimmune reagents and could only be inhibited by preincubation with the IgEf used for immunization and not with dog immunoglobulin G, E. coli extract, or with a nonrelevant recombinant [His]6-tagged protein. In immunohistochemistry, the IgEf3/4-specific Ab specifically recognized cells in paraffin-embedded tissue sections of lymph nodes. Furthermore, both of the IgEf-specific Ab elicited positive immediate type 1 skin reactions in dogs. Semiquantitative assessment of total serum IgE in dogs was developed using IgEf2-specific Ab as coating reagent and the biotinylated IgEf3/4-specific Ab as developing Ab in ELISA. In conclusion, both IgEf-specific Ab recognize native dog IgE with the advantages that they are directed against different and known constant domains of the IgE molecule, and that they can be used for immunohistochemistry on paraffin-embedded tissue. The two dog IgE-specific Ab could initiate clinical research on the involvement of immediate-type hypersensitivity reactions in dogs.
Animals↗
Allergen standardization at a crossroads?
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Allergens↗
Basophil histamine release and leukotriene production in response to anti-IgE and anti-IgE receptor antibodies. Comparison of normal subjects and patients with urticaria, atopic dermatitis or bronchial asthma.
The IgE receptor-dependent in vitro mediator release in basophils is characterized by a large interindividual variability both in normal and atopic subjects. The mechanism and the clinical impact of this finding, however, is largely unclear. The aim of the present study was to examine the role of surface-bound IgE and of response-modifying cytokines such as interleukin 3 (IL-3) as possible factors determining basophil releasability in atopic patients and normal controls. Cells from 30 individuals (6 with urticaria, 7 with asthma, 7 with atopic dermatitis, and 30 healthy controls) were isolated and stimulated for mediator release by IL-3 and different triggering antibodies directed against IgE or IgE receptor. Our data suggest that serum IgE levels and basophil receptor occupancy with IgE are not involved in the mechanism of basophil releasability. Furthermore, IL-3-induced similar effects on mediator release in almost all individuals, rather excluding the possibility that releasability is regulated by cytokine priming of basophils. Interestingly, we found that patients with atopic disease have a reduced capacity of releasing mediators upon activation, the mechanism of which is unclear. In conclusion, our findings support the hypothesis that basophil releasability is dependent on cell-imminent mechanisms in basophils, which may be altered in selected atopic patients.
Adult↗
Food allergy: problems, fiction and hard facts.
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Allergy and Immunology↗
Anti-IgE autoantibodies and bee-sting allergy.
Serum anti-IgE autoantibodies (aaIgE) were investigated by dot immunobinding assay in bee-allergic patients in comparison with nonallergic beekeepers, healthy blood donors, and atopic subjects. Elevated serum levels of aaIgE--either free or combined with IgE--were found in both bee-allergic patients and atopic subjects as compared with beekeepers and healthy donors. With regard to a possible significance of aaIgE for the protective mechanism induced by specific allergen immunotherapy, we estimated aaIgE in bee-allergic patients before, during, and after bee-venom immunotherapy (BVIT) in relation to the outcome of a provocation test with a living bee (PT). During the first year of BVIT, there was no significant change in either free or combined aaIgE, but aaIgE decreased during protracted BVIT over 3-7 years. By using two monoclonal anti-IgE antibodies with different epitope specificity (Le27 and BSW17), we were able to detect two kinds of IgE/aaIgE immune complexes. Our data show that during and after BVIT the levels of one kind of IgE-aaIgE immune complex (the non-BSW17 type) tended to decrease in PT-negative patients but stayed elevated in PT-positive patients. The levels of the other kind of immune complex (the non-Le27 type) were similar in treatment failures and successfully treated patients. These data suggest that there are various kinds of aaIgE with different in vivo functions related to their epitope specificity. Some of them (non-BSW17 type) might be associated with BVIT failure.
Adult↗
Farewell address. 40 years allergo-immunology: from the nipple unto milk.
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Allergy and Immunology↗
Critical evaluation of the use of skin tests and cellular tests in standardization of allergens.
In two groups of 8 and 40 allergic patients repeatedly skin-tested with various dilutions of timothy allergen and with histamine (10 mg/ml) intradermally and by prick test, the skin reactions were evaluated by wheal and erythema size at 20 minutes and kinetically followed over 60 minutes by infrared telethermography. The latter technique permits to define further reaction parameters, such as thermographic area and Thermographic Units based on the average elevation of temperature in the reaction site. These studies have led to several conclusions. First, the skin area really involved in skin reactions to allergens or to histamine are much larger than assessed visually. There is more to it than meets the eye. Second, among all parameters studied in terms of reproducibility upon repeated testing, erythema and thermographic areas are the most stable, while wheal area shows considerably larger variations. Third, there is no good correlation between reactions to allergen dilutions and reactions to histamine, either individually or as groups of patients. In addition, the ratio of thermographic area (as true indication of allergic inflammation) to erythema area and the kinetics of the reaction are very different between allergen-induced and histamine-induced reactions. There is therefore no real advantage in relating reactions to allergen to reactions to histamine, in terms of biological standardization. Fourth, the intradermal technique, in terms of reactions to histamine, definitely shows better reproducibility than the prick test technique in skilled hands. A method such as the HEP standardization technique, combining prick testing, evaluation of skin reactions by wheal area and reference to a histamine standard is therefore the worst of possible alternatives. The US method, based on intradermal injection of various dilutions of allergen and evaluation of erythema, seems to us more adequate and reproducible for quantitative biological standardization of allergen extracts by skin testing. This statement does not mean that prick testing could not nevertheless be considered as a method of choice for diagnostic skin testing.
Allergens↗
[Allergology general practice in Switzerland: present and future].
The conditions of an allergological evaluation was determined in Switzerland, based on a questionnaire (1535 physicians and 648 pharmacists, of whom 33% answered). Besides dermatologists and allergists, ENT specialists are most frequently confronted with allergological problems. Serological determination of IgE are performed more frequently than skin tests, specifically by specialists for internal medicine and paediatrics. Pharmacists are quite often asked for remedies and tend to use alternative medical approaches more frequently than physicians. The data show that the specialty of allergology is changing and that, along with the high frequency of allergological patients, many non-allergologists participate in their treatment. The allergist of the future will deal more with complicated cases and be on the front line for establishing new diagnostic tools and therapies.
Allergy and Immunology↗
Cytokines in allergic inflammation.
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Chemotactic Factors↗
Immunochemical particularities of anaphylactic reactions to compounds used in anesthesia.
The main compounds causing anaphylactic reactions in anaesthesia are myorelaxants, opiate or barbiturate derivatives or natural allergens (latex). While the latex-derived allergens are of sizeable molecular weight and behave as regular complete allergens, most of the other compounds are low molecular weight molecules behaving as incomplete allergens or haptens. For these, the sensitization process usually encompasses direct reaction (conjugation) with cellular surface proteins (e.g. histocompatibility antigens) of an antigen-presenting cells and ensuing formation of hapten-specific IgE antibodies. Since many patients experience igE-mediated anaphylactic reactions upon first contact with a myorelaxant, a previous latent sensitivity to some cross-reactive epitope (e.g. quaternary ammonium group) must be postulated. In sensitized individuals possessing drug-specific IgE antibodies, the elicitation of anaphylactic reactions classically requires bridging on the surface of IgE loaded mast cells/basophils by allergens which are functionally at least bivalent (two or more reactive epitopes by allergen molecule). In some cases, myorelaxant molecules, chemically appearing as mirror molecules may be functionally bivalent and elicit anaphylactic reactions apparently directly. In most instances, however, when the responsible drug only contains one reactive epitope per molecule, alternative mechanisms and rapid formation of functionally polyvalent drug allergens in tissue have to be postulated in order to explain the rapid elicitation of anaphylactic reactions by molecules which appear to be immunologically monovalent in vitro. Indeed, in most instances, monovalent haptens and drugs appear to be inhibitors rather than elicitors of IgE-mediated reactions.
Anaphylaxis↗