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Prevention of allergic sensitization to beta-lactoglobulin with conjugates made of beta-lactoglobulin coupled to isologous immunoglobulin G.

We have shown that, under certain conditions, a single dose of a conjugate of beta-lactoglobulin linked to isologous IgG suppresses specific antibody responses (IgE, IgG, and IgA) in rats immunized with beta-lactoglobulin. This suppression is allergen specific. It also appears to be effective when animals are first immunized and then tolerized. In addition, administration of the beta-lactoglobulin-IgG tolerogen abolishes mast cell mediator release. This has been shown both in vivo and with passively sensitized mast cells in vitro. We propose that the construction of a tolerogen made of whole protein allergen linked to IgG could provide a novel specific therapy for allergic reactions.

Animals↗

Demonstration of auto-anti-idiotypic antibody cross-reacting with public idiotypic determinants in the serum of rye-sensitive allergic patients.

The present study documents the presence, in the serum of one allergic individual, of auto-anti-idiotypic antibodies cross-reacting with public idiotypic determinants expressed on human IgE and IgG anti-Rye I antibodies. Sera from rye-sensitive patients were tested for specific IgG and IgE antibodies to Rye I by double antibody. The IgG fraction, isolated from the serum of a patient with a history of previous hyposensitization therapy, was repeatedly absorbed on Rye-I-Sepharose as well as on IgM- and IgG-Sepharose to remove anti-Rye I antibodies as well as any possible anti-heavy or light chain activity. This IgG fraction, named anti-idiotypic fraction (a-IdF), blocked in a dose-dependent fashion the reaction of IgG and IgE anti-Rye I antibodies with Rye I antigen. The a-IdF also blocked the binding of anti-rye antibodies to Rye I antigen in the serum of 20 unrelated allergic patients, indicating that these anti-Rye I antibodies bore public idiotypic determinants.

Adolescent↗

Prevalence of allergic sensitization to inhalant allergens among blood donors in Kuwait--a desert country.

Kuwait is a desert country where the prevailing high temperatures, low humidity, and scant vegetation suggest a low prevalence of allergy. We evaluated the prevalence of atopic sensitization (presence of allergen-specific IgE) among young adult blood donors by screening a total of 505 subjects (male: female ratio 1.6) with mean age of 28.4 years (range 18-50 years). The Pharmacia CAP-Phadiatop test, which detects serum IgE specific to most common airborne allergens, was used. Some of the specific sensitizing allergens were also identified by the related CAP-RAST method. Sensitization was detected in 223 of the 505 subjects (44.2%) screened. Kuwaiti nationals had a significantly higher prevalence rate (50.2%) than non-Kuwaitis (34.2%) (chi 2 = 8.6, P < 0.003). The highest prevalence rate was found among male Kuwaitis (53.8%). The prevalence of current or previous allergic disease (subject-reported) was 20.6%. Bermuda grass, house-dust mite (Dermatophagoides pteronyssinus), and Chenopodium album were the most prevalent sensitizing allergens, with frequencies of 53.6%, 52.7%, and 50.9%, respectively, among the sensitized subjects (corresponding to 23.7%, 23.3%, and 22.5%, respectively) for the entire population. Sensitization increased with age, but only among the expatriates, younger Kuwaitis being as frequently sensitized as the older ones. Polysensitization was found to be common. Of the 109 CAP-RAST-positive subjects, 71 (65.1%) were sensitized to more than one allergen, and 30 of these (42.3%) were sensitized to four or more allergens. These results show that atopy is highly prevalent among young adults in Kuwait, and the higher prevalence rate among nationals than expatriates suggests the involvement of genetic or local environmental factors. The results also confirm that mite and plant pollens may be major sensitizing allergens even in a desert environment.

Adolescent↗

Rethinking Th2 antibody responses and allergic sensitization.

Human Th2 cytokines (interleukins 4 and 13) induce co-expression of IgE and IgG4 through sequential switching. The regulation of IgG4 responses and the role of these responses in the pathogenesis of allergy have not been characterized. We are addressing these issues by comparing and contrasting the expression of allergen-specific IgE and IgG4 in a population of European children thoroughly defined for lifestyle, environmental exposures and allergic phenotypes. The current analysis focused exclusively on children from non-farming families (n=493) in order to avoid potential effects of exposure to microbial products abundant in farming environments. We found that allergens induce Th2-mediated IgG4 and/or IgE responses in the majority of the population. Approximately two-thirds of the children had allergen-specific IgG4 but not IgE, only a minority had both IgG4 and IgE, only a few were negative for both, and virtually none had only IgE. The prevalence of asthma and hay fever was dramatically higher in children with high IgG4 and IgE compared to children who only mounted IgG4 or low IgG4 and IgE responses. These results appear to recapitulate different stages of in vivo Th2-dependent sequential switching from IgG4 to IgE. These patterns of Th2-induced antibody responses may warrant a redefinition of the notion of allergen sensitization.

Agriculture↗

Adjuvant effect of respiratory irritation on pulmonary allergic sensitization: time and site dependency.

It has been suggested that airway irritation, by acting as an adjuvant, as well as producing damage, may be an important factor related to asthma. The present study examined the window of time following acute upper and lower airway irritant exposure to determine the period of increased risk of immunological sensitization. Brown Norway rats were exposed to 87 ppm NO2 or 1000 ppm NH3 for 1 hr. A 30-min ovalbumin (OVA) exposure of 18.14 microg/liter air was given at various times based upon the time course of irritant associated inflammatory response (either immediately prior to or 1 or 7 days after the irritant exposure). OVA-only, NO2-only or NH3-only controls, and saline controls were also studied. Weekly booster exposures of OVA (or saline) were given. Circulating OVA-specific IgE, IgA, and IgG levels were quantified periodically during the 6 weeks of the study. Bronchoalveolar lavage (BAL) was also performed to examine the inflammatory response to allergic and irritant challenge. Significant increases in OVA-specific IgE, IgG, and IgA antibody titers were seen in rats given the sensitizing OVA exposure within 1 day of the NO2, but not NH3 exposures. Enhancement of cellular infiltrate in BAL was noted in groups given the sensitizing OVA exposure within 1 day of the NO2 or NH3. It is concluded that the inflammatory and immunological response to antigen exposure can be modified by the site of respiratory tract irritation and the relative times of irritant and antigen exposure.

Adjuvants, Immunologic↗

[Allergic sensitization and latex-associated symptoms in a group of health workers].

The presence of symptoms connected with the use of latex rubber gloves and sensitization to this allergen was studied in a group of 660 hospital workers who regularly used gloves as a means of protection. Symptoms connected with the use of gloves were reported by 153 subjects (23.2%) and were significantly associated with female subjects length of use and type of medical care. The majority of cases reported irritative symptoms (13.2%) whereas contact dermatitis and rash were reported by 3.6% and 5.5% of cases respectively. Systemic reactions (asthma and/or rhinitis) were reported by 5 subjects. Prick tests for latex were positive in 23 cases (3.5%), 15 of which were symptomatic. Positive skin reaction to latex was significantly associated with family atopy, personal case history and prick test. It is concluded that the presence of symptoms and sensitization to latex requires the implementation of preventive measures in order to reduce the risk of sensitization to a minimum, in addition to removal from exposure of those subjects who are already symptomatic or at risk.

Adult↗

Asthma and rhinitis in schoolchildren: the impact of allergic sensitization to aeroallergens.

This study aimed to evaluate the prevalence of asthma and rhinitis in schoolchildren living in the Genoa area by using a validated questionnaire and to investigate the prevalence of sensitizations using skin prick tests. An ATS modified questionnaire was given to 781 schoolchildren (all of them aged between 11 and 14 years) resident in the Genoa area. The main outcome of the present survey demonstrates a high prevalence of sensitized children (40.7%). Asthma and rhinitis prevalences are very high, mainly concerning the lifetime diagnosis. Actual asthma prevalence is about 6%, confirming ISAAC results, but rhinitis prevalence is notably higher and there is no difference between seasonal and perennial forms. Mites are the most important cause of sensitization and pollens are more frequently the cause of polysensitization. A distinct percentage of the asthmatic children and a higher percentage of rhinitic children are nonallergic. On the other hand, about one third of the sensitized children are without symptoms: They may be considered as subjects at risk of developing clinical respiratory diseases later. In conclusion, this study shows the importance of evaluating the existence of atopy, since there are many subjects with asthma and rhinitis who are nonallergic, and subjects at risk of developing respiratory allergies may be detected.

Adolescent↗

The capacity of particles to increase allergic sensitization is predicted by particle number and surface area, not by particle mass.

Particle exposure has traditionally been monitored as mass concentration of PM10 (particles with an aerodynamic diameter less than 10 microm), more recently also as PM2.5. The mass concentration is strongly influenced by the large particles. Therefore, particle mass is a poor measure for characterizing the amount of the small, possibly more biologically potent particles. We used polystyrene particles (PSP) ranging in diameter from 0.0588 to 11.14 microm, carbon black (CB), and diesel exhaust particles (DEP), to study the adjuvant effect of particles on the immune response to the allergen ovalbumin (OVA) after sc injection into the footpad of BALB/cA mice. At a given mass dose, the small particles (0.0588 and 0.202 microm PSP, CB, and DEP) increased the allergen-specific IgE serum levels to a substantially higher degree than the larger particles (1.053, 4.64, and 11.14 microm PSP). Further, in the draining lymph node during the primary response, the fine particles (0.202 microm) with OVA increased cell numbers, expression of surface markers (CD19, MHC class II, CD86, and CD23) and ex vivo production of IL-4 and IL-10, whereas the largest (11.14 microm) particles did not. Linear regression analyses indicated that the IgE response was not predicted by particle mass (R2 = 0.06), but was predicted by the total particle surface area (R2 = 0.64), number of particles (R2 = 0.62), and particle diameter (R2 = 0.58). In conclusion, we found that fine particles exerted stronger adjuvant effects on allergic responses than larger particles at equal mass doses. Consequently, the dose described as total particle surface area or particle number predicts the adjuvant effect of particles better than the currently used particle mass.

Adjuvants, Immunologic↗

[Evaluation of allergic sensitivity to the virkon disinfectant preparation widely used in Poland].

The aim of the study was to define the sensitising effect of Virkon, a disinfectant widely used in Poland, especially in hospitals. The study was carried out on guinea pigs, using the maximisation test according to Magnusson and Kligman, modified by Krysiak. The assessment of dermal changes presented in the percentage of sensitised animals, being thus far the criterion adopted by Magnusson and Kligman, has been expanded to include our own criteria covering the intensity of reactions of testing samples and the results of eosinophilic and basophilic tests in peripheral blood. Using these parameters and applying pathomorphological examinations it was possible to indicate the difference in the intensity of sensitising effect of Virkon, depending on the concentration used. The results of the study showed that 1% aqueous solution of Virkon is the optimum concentration for monitoring its sensitising effects in people having contact with this substance.

Animals↗

Blockade of CTLA-4 enhances allergic sensitization and eosinophilic airway inflammation in genetically predisposed mice.

CTLA-4 (CD152) expression is restricted to subsets of activated T lymphocytes and shares homology with CD28. CTLA-4 and CD28 molecules both bind to B7 molecules on antigen-presenting cells. Whereas CD28-B7 interaction enhances T cell activation, cytokine production and survival, CTLA-4 signaling down-regulates T cell responses. Here, we studied the involvement of CTLA-4 triggering in the pathogenesis of allergen-induced airway inflammation in mice. Anti-CTLA-4 mAb were injected during i.p. sensitization with ovalbumin (OVA). This treatment favored OVA-specific IgE production and augmented blood eosinophilia in BALB/c mice. In BALB/c mice, enhanced Th2 sensitization after anti-CTLA-4 mAb injections resulted in more severe airway inflammation, and increased airway hyperresponsiveness to metacholine, bronchial eosinophilia and IL-4 and IL-5 levels in broncho-alveolar lavage (BAL) fluid following repeated allergen inhalations. Importantly, aggravation of airway inflammation and enhancement of Th2 responses were accompanied by a significant reduction of pulmonary TGF-beta levels at protein level in BAL fluid as well as on mRNA level in inflamed lung tissue. In contrast to BALB/c mice, blockade of CTLA-4 did not alter IgE production nor the phenotype of airway inflammation or TGF-beta production in C57BL/6 mice. Our data suggest that CTLA-4 triggering represents an important regulatory mechanism for Th2 sensitization in genetically predisposed mice by modulating TGF-beta production.

Abatacept↗