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PubMed1994

Novel fundamental approaches to intervening in IgE-mediated allergic diseases.

Recent progress in our understanding of the immunologic basis of allergic diseases has suggested that enhanced production of the cytokines IL-4 and IL-13 by allergen-specific T cells is responsible for increased IgE synthesis and the development of allergic disease in certain individuals. Based on these observations, it is clear that approaches to inhibition of allergen-specific IgE synthesis should be aimed at blocking the activation or preventing the synthesis of IL-4 and IL-13. In the present review, two approaches toward this goal are discussed. First, an IL-4 mutant protein is described that acts as a powerful antagonist of both IL-4 and IL-13 activity, including induction of IgE synthesis by these cytokines in vitro. Second, it is demonstrated that T-cell clones can be rendered non-responsive following incubation with allergen-derived peptides representing minimal T-cell activation-inducing epitopes. These non-responsive T cells fail to produce IL-4 and IL-13 and to proliferate following subsequent activation with the relevant allergen and antigen-presenting cells. In addition, these non-responsive T cells fail to provide B-cell help for IgE synthesis. It is tempting to speculate that induction of non-responsiveness in allergen-specific T-cell clones by allergen-derived immunogenic peptides may provide the basis for successful desensitization of allergic patients.

Desensitization, Immunologic↗

PubMed1976

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.

Adsorption↗

PubMed1995

Phenomenology, pathogenesis, diagnosis and treatment of aspirin-sensitive rhinosinusitis.

Aspirin-sensitive rhinosinusitis is a non-allergic, non-infectious perennial eosinophilic rhinitis starting in middle age and rarely seen in children. It may also been seen in atopic patients who have developed a mixed type rhinitis with recurrent airway infections. There is an intolerance to aspirin and most other NSAID. An intolerance to tartrazine, food additives, alcohol, narcotics and local anaesthetics can follow. Most aspirin-sensitive patients develop nasal polyps. Untreated, it can lead to asthma. The frequency of aspirin intolerance is 6.18% in patients with perennial rhinitis and 14.68% in patients with nasal polyps. Immunologic studies of the blood and the nasal polyps show a hyperreactive immune system with an activation of the eosinophil granulocytes due to a TH1-lymphocyte-activation. In atopic subjects with a mixed type rhinitis, we found a TH2- and B-lymphocyte-activation as well. Inhibition of eosinophil apoptosis might be a second remarkable change in the immune system of aspirin-sensitive patients. A key pathogenic event for aspirin sensitivity is the change of the leukotriene pathway for arachidonic acid metabolism releasing high amounts of leukotrienes LTC4, LTD4 and LTE4, effective chemoattractants and activators of inflammatory cells. For the diagnosis of aspirin intolerance, nasal, bronchial and oral challenge are available. The sensitivity of nasal challenge with lysine-aspirin for the diagnosis of aspirin-sensitive rhinitis is 0.93, the specificity 0.97. It is the safest test in aspirin-sensitive asthmatics causing bronchial side effects only in 0.45%. Therapy of aspirin-sensitive rhinosinusitis includes avoidance of aspirin and NSAID. A general down regulation of the immune response with glucocorticosteroids is an effective means. We prefer a maintenance dose of budesonid 400 micrograms a day. Systemic steroids for a reversibility test or in exacerbation due to viral infection are given in a dose of 50 mg a day for one week. If steroids don't work well enough, we combine them with aspirin desensitizations at a maintenance dose of 500 mg a day. Gastrointestinal side effects occur in 20% of the patients with a dose of 500 mg aspirin a day, in 46% with a mean dose of 1300 mg a day. The combined treatment of topical nasal steroids and aspirin-desensitization is effective in 65% of the patients with improvement in the symptoms of hyper-secretion, irritation and blockage, while 73% show improvement of polyps, hyposmia and anosmia. Endonasal endoscopic surgery of the ethmoids, turbinectoms and septoplasty should be done if necessary, especially in cases where conservative treatment fails. After surgery a further antiinflammatory treatment is absolutely necessary otherwise polyps reoccur in 90% of the cases after weeks or months. Unfortunately there is so far no curative treatment. New drugs like cytokine or leukotriene receptor antagonists give hope for better results in treatment of aspirin intolerance in the future.

Adrenal Cortex Hormones↗

PubMed1989

Immunologic and clinical evaluation of a 12-month course of specific immunotherapy.

Allergen specific immunoglobulins (IgE, IgG, IgG1, and IgG4) were evaluated during the course of a 12-month specific immunotherapy (ITS) in 27 allergic subjects: 12 Dermatophagoides pteronyssinus (DP)-, 9 Parietaria officinalis (W19)-, six perennial and timothy rye grass (G5 and G6)-sensitive cases. Further, the modifications of the specific Ig levels were compared with the significant improvement in symptoms and drug consumption observed after 12 months of ITS. IgE levels significantly decreased after 6 and 12 months, while IgG1 significantly increased in the early phases of ITS (3rd month), and IgG4 significantly and progressively increased during the course of ITS. No modification was observed in specific total IgG. Regression analysis test among the various Ig levels revealed a strict correlation only between IgE and IgG4 (high levels of IgE before ITS correlated with high levels of IgG4 after 12 months of ITS). No correlation was observed between total Ig changes and improvement of clinical status or drug consumption.

Adolescent↗

PubMed1987

Assessment of prolonged venom immunotherapy in children.

Venom immunotherapy was initiated in 94 children from April 1977 to October 1979. As of February 1983, 66 children had continued receiving treatment and had recent immunologic evaluation. Assessment of prolonged venom treatment included analysis of immunologic parameters, efficacy of treatment, and long-term safety. Venom skin tests, venom-specific IgE antibody levels, and venom-specific IgG antibody levels comprised the immunologic parameters evaluated. A decrease in allergic sensitivity was demonstrated over time in the skin and serum. Forty-three of 57 (75%) children had less positive vespid venom skin tests, and the mean venom-specific IgE antibody level declined to less than the pretreatment value with 3 or more years of yellow jacket venom therapy. Venom-specific IgG antibody measurements rose rapidly after the initiation of venom injections and were maintained for the duration of this evaluation. During a 3- to 6-year period, 200 stings in 49 treated children resulted in only four mild systemic reactions (98% efficacy). The benign nature of interval histories, physical examinations, and laboratory analyses in these children argues optimistically for the safety of prolonged venom immunotherapy.

Adolescent↗

PubMed2005

Inhibition of allergen-induced airway inflammation and hyperreactivity by recombinant lactic-acid bacteria.

Recombinant lactic-acid bacteria (LAB) are able to inhibit allergen-specific T-cell responses. In this study, we examined whether oral feeding of recombinant LAB was able to suppress allergen-induced airway inflammation and hyperreactivity (AHR) in a murine model. Animals were intraperitoneally sensitized with Dermatophagoides pteronyssinus group-5 allergen (Der p 5) and orally treated with recombinant LAB containing a plasmid-encoded Der p 5 gene or placebo on day 7 and day 14 for three days consecutively. Twenty-one days after sensitization, mice underwent inhalational challenging. Der p 5-specific immunological responses including changes to specific immunoglobulin G and E (IgE) levels, the presence of cells in the bronchoalveolar lavage fluid (BALF), and AHR were assessed following this inhalational challenge. We demonstrated that oral feeding of recombinant LAB could significantly decrease the synthesis of Der p 5-specific IgE, and AHR. Furthermore, following such treatment, we also noted that both neutrophils and eosinophils had infiltrated the BALF to a significantly lower extent, when compared to the vehicle-treated group. Neither recombinant allergen nor LAB alone was able to suppress allergen-induced immune responses. Our findings suggest that treatment with recombinant LAB at a low dose can suppress allergen-induced airway allergic inflammation, this providing a basis for developing a novel therapeutic method for allergic airway diseases.

Administration, Oral↗

PubMed1994

[Allergic reactions of the respiratory tract].

Allergic rhinoconjunctivitis and allergic asthma bronchiale are immunologically mediated diseases of the respiratory tract. Dependent on the allergen, they occur seasonally or perennially. Allergens can cause a specific reaction of the immune system, mediated by IgE-antibodies in individuals with a genetic predisposition. Different mediators are released from mast cells, and complex immunopathological mechanisms lead to inflammatory changes of the mucosa. A significant increase of allergies has been observed in the last decades. Indoor and outdoor allergens can be differentiated. Mites and animal dander are the most important indoor allergens. The pollens of birch, alder, hazel, different grasses and mugwort are the most important outdoor allergens. For diagnostic purposes skin tests, laboratory analyses and provocation tests are used. The best therapy is elimination of the offending allergen. As pharmacological agents histamine-receptor antagonists, topical corticosteroids and topical cromoglycate are currently used. Immune therapy is the most specific form of treatment.

Allergens↗

PubMed1984

Prevention of food allergies.

Any rational approach to the prevention of food allergies must be based on the diversity of mechanisms which are involved in their pathogenesis. In addition to the IgE-mediated disorders which appear to be responsible for the largest number of cases, other immunologic (e.g., immune complex) and non-immunologic (e.g., enzymatic deficiencies) mechanisms appear to be involved. A preventive program should begin with a recognition that a potential problem exists and the identification of the individual at risk. This is accomplished by a careful documentation of IgE or other allergic reactivity in the individual or in family members. The prevention of intrauterine or postnatal sensitization is achieved by reduction in antigen transfer to the infant by maternal avoidance of potentially allergic foods in the last trimester and during lactation and by a restrictive infant diet. During the first years of infancy the encouragement of breast-feeding provides the dual benefit of eliminating one of the most common sensitizing food antigens, i.e., cow's milk protein, and providing passive s-IgA. The use of appropriate pharmacologic agents, e.g., cromolyn, may be yet another valuable adjunct in the prevention of food allergy.

Antigen-Antibody Complex↗

PubMedDate not supplied

[Latex allergy. Diagnosis and therapeutic aspects].

In the last two decades of the 20th century, latex allergy has reached epidemic proportions. Epidemiological studies demonstrate that 3-25 % of health personnel is allergic to latex. The main risk groups are health workers, machine operators in latex factories, and children with spina bifida and urogenital anomalies. From the allergenic point of view, latex contains 240 peptides but approximately 50 are able to react to IgE. Latex elongation factor Hevdl is the relevant allergen in patients with spina bifida. Prohevein (hev B6) behaves as a major allergen, since it reacts to IgE in most of the sera of patients with latex allergy. The nature of latex is complex; it is an allergenic mixture that depends on chemical, immunological and epidemiological variables. Latex proteins show strong cross reactivity with several proteins from fruit and vegetable grains such as avocado, potato, banana, tomato, chestnut, and kiwi. In vivo studies have shown that class I chitinase from avocado and chestnut behave as major allergens in allergic patients with latex-fruit syndrome. The clinical manifestations related to the use of latex products depend on the type of exposure, the amount of the allergen, and individual variability. The most useful diagnostic method is the skin prick test. Several perioperative guidelines are recommended in patients sensitized to latex as well as various alternatives to rubber gloves. An increasing number of studies describe the efficacy of etiological treatment (immunotherapy), using different guidelines and routes of administration. These preliminary data encourage the hope that in the near future immunomodulatory therapy will be available to mitigate against the latex allergy epidemic.

Adult↗

PubMed2006

Dose dependence of efficacy but not of safety in sublingual immunotherapy.

Sublingual immunotherapy (SLIT) currently represents, as indicated by meta-analysis of its efficacy and safety, a valid option to the generally used traditional subcutaneous immunotherapy (SCIT) for treating respiratory allergy. Regarding efficacy, recent studies demonstrated that, similar to what has already been observed in SCIT as well as in experimental and clinical studies about the magnitudo of allergen exposure, the effectiveness on both clinical symptoms and immunologic changes depends on the amount of allergen administered during treatment. In addition, in vitro studies addressed with the role of dendritic cells, currently considered to be of pivotal importance in orienting toward tolerance the immune response to allergens, showed that the internalisation of allergen molecules, which is followed by tolerogenic presentation to T cells, depends on the amount of allergen. However, such dose dependence is not apparent concerning the safety. In fact, the comparison of studies respectively conducted with high and low allergen doses did not show differences in the rate of systemic reactions, which in any case never had the presentation of anaphylaxis, and instead a significant difference in the rate of local reactions, following the oral and gastrointestinal contact with the allergen extract, in favour of high dose studies.

Administration, Sublingual↗

PubMed2006

Specific oral tolerance induction in food allergy.

Specific oral tolerance in food allergy can be induced by oral administration of the offending food, starting with very low dosages, gradually increasing the daily dosage up to an amount equivalent to a usually relevant dose for daily intake, followed up by a daily maintenance dose. Unfortunately, the body of scientific evidence concerning specific oral tolerance induction (SOTI) is still rather poor. Following a couple of case reports, only a few studies on a limited number of patients including different allergens are available. So far, no placebo-controlled, long-term study has been published. Concerning the underlying immunological mechanism, a limited number of studies have reported on changes in antibody production, and more recently on the role of different T-cell populations. The individual pattern of clinical reaction during SOTI seems to vary considerably between patients and from allergen to allergen. Arguments in favour of SOTI are the safety for an inadvertent intake of the offending food and the increased quality of life. Arguments against SOTI are the necessity for a regular intake and possible long-term compliance problems. Indications to consider SOTI in the future might be (i) importance of the incriminated food for the individual nutritional regimen, (ii) avoidance of the corresponding food cannot be assured and (iii) persistent severe food allergy. However, before SOTI can be recommended for the daily praxis, more studies are warranted to clarify whether certain patients may profit from SOTI and to understand the underlying mechanism.

Animals↗

PubMed2000

Pilot study of IFN-gamma-induced specific hyposensitization for house dust mites in atopic dermatitis: IFN-gamma-induced immune deviation as a new therapeutic concept for atopic dermatitis.

IFN-gamma/IL-4 imbalance is a central immunologic defect which is responsible for increased IgE antibody response in atopic dermatitis. Effects of hyposensitization were controversial in atopic dermatitis. Reversed IFN-gamma/IL-4 balance was induced using IFN-gamma in atopic dermatitis and specific hyposensitization with house dust mites (HDM) was tried in the status of IFN-gamma-induced immune deviation. A total of 58 atopic dermatitis patients who had obvious allergy to HDM were selected in this study. IFN-gamma-induced hyposensitization for HDM was tried in 10 patients. Twenty-two patients received IFN-gamma therapy and six were treated by simple hyposensitization. Twenty were enrolled as control subjects. The clinical severity scores decreased effectively only by IFN-gamma-induced hyposensitization for HDM. Specific hyposensitization for HDM in the status of IFN-gamma-induced immune deviation successfully improved atopic dermatitis. HDM might play a pathogenic role in subpopulation of atopic dermatitis.

Adolescent↗

PubMed1983

Epidemiologic study of insect allergy in children. II. Effect of accidental stings in allergic children.

One hundred eighty-one children with non-life-threatening reactions to insect stings and positive venom skin tests were randomized to treatment (53) or no-treatment (128) groups and followed up clinically and immunologically for at least two years to assess the results of accidental stings. Twenty-eight stings in 17 treated patients and 74 stings in 47 untreated children occurred, leading to one mild reaction in a treated patient, and eight in the no-treatment group (P = NS). No reaction was more serious than the original. Based on IgE antibody changes and skin test results, 87% of the untreated children were stung by an insect to which they had clinical sensitivity by skin test. Vespid skin test sensitivity decreased 10-fold or more in both treated (72%) and untreated (44%) children. Of those with increased sensitivity, congruent to 70% had been stung. These data indicate that the incidence of severe reactions on resting is low in insect-allergic children, and that the majority show decreased skin test sensitivity over time.

Adolescent↗

PubMedDate not supplied

Comparative clinical-immunological study of oral and subcutaneous immunotherapy in children with extrinsic bronchial asthma.

There is discrepancy of criteria regarding the clinical immunological efficacy of allergenic extracts, administered by oral way, for the control of allergic symptoms of the respiratory airways. The predominant mono-sensitization to D. pteronyssinus and the early development of allergic respiratory symptoms in our medium motivated us to evaluate the clinical-immunological efficacy of oral immunotherapy in children with bronchial asthma. Twenty-eight patients affected with extrinsic bronchial asthma to D. pteronyssinus were included in our study; their average age was 27.93 months (range between 18-42 months) and the SD (standard deviation), 5.46. For the reception of oral and subcutaneous vaccines, made-up of 100% D. pteronyssinus, the patients were divided into two groups of 14 children each. The clinical immunological evaluation was realized in basal conditions, 6 and 12 months after the initiation of both vaccines. IgE and seric IgG4 against D. pteronyssinus was quantified through RAST. The results obtained were as follows: 1. Subcutaneous immunotherapy (SI) was seen to be more effective than oral immunotherapy (OI), throughout the 12 months of the study. 2. In both vaccines, the IgE against D. pteronyssinus did not undergo any statistically significant changes (p less than 0.766 and p less than 0.246). 3. IgG4 against D. pteronyssinus increased more with subcutaneous than with oral therapy. There were statistically significant differences for both kinds of therapy at 6 and 12 months, the difference between basal and 12 months being p less than 0.001 and p less than 0.020, for subcutaneous and oral therapy respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed2007

A recombinant allergen chimer as novel mucosal vaccine candidate for prevention of multi-sensitivities.

BACKGROUND: As conventional immunotherapy is less efficacious in patients with allergic multi-sensitivities compared with mono-sensitized subjects, new intervention strategies are needed. Therefore, an allergen chimer was genetically engineered for treatment of multi-sensitization with birch and grass pollen on the basis of mucosal tolerance induction. METHODS: The major birch pollen allergen Bet v 1 served as a scaffold for N- and C-terminal linkage of the immunodominant peptides of the grass pollen allergens Phl p 1 and Phl p 5 and this new construct was cloned and expressed in Escherichia coli. After purification, physicochemical and immunological characterization the chimer was used for intranasal tolerance induction prior to poly-sensitization with Bet v 1, Phl p 1 and Phl p 5. RESULTS: The immunological characterization revealed that the conformation of Bet v 1 within the chimer was comparable to that of natural as well as recombinant Bet v 1. The chimer was immunogenic in mice for T and B cell responses to the three allergens. Intranasal application of the chimer prior to poly-sensitization significantly suppressed humoral and cellular allergen-specific Th2 responses and prevented development of airway inflammation upon allergen challenge. Moreover, local allergen-specific IgA antibodies were induced by the chimer. The mechanisms of poly-tolerance induction seemed to be mediated by regulatory cytokines, since TGF-beta and IL-10 mRNA in splenocytes were upregulated and tolerance was transferable with these cells. CONCLUSION: The data indicate that such allergen chimers harboring several unrelated allergens or allergen peptides could serve as mucosal polyvalent vaccines for prevention of multi-sensitivities.

Administration, Intranasal↗

PubMedDate not supplied

Serum IFN-gamma and IL-10 levels before and after specific immunotherapy in patients with allergic rhinitis.

Although a detailed explanation of the mechanism of immunotherapy is not known, several immunologic explanation have been proposed. It's said that T cell-cytokine profile changed with allergen immunotherapy. In our study we evaluated IFN-* and IL-10 levels before and after immunotherapy in patients with allergic rhinitis. Twenty patients (mean age; 27.3 +/- 4.84), 8 male, 12 female with allergic rhinitis, mean duration of disease was 5.55 +/- 1.23 years and 13 healthy controls, 5 male, 8 female (mean age: 28.38 +/- 5.61) were enrolled in the study. Immunotherapy was performed for grass pollen allergen extract to patients with allergic rhinitis for 31.5 +/- 4.98 months. Serum IL-10 and IFN-* levels were evaluated with ELISA. Serum IL-10 levels were significantly high before and after immunotherapy compared to controls. There was no difference in IFN-* levels before and after SIT compared to controls. According to this study, in patients with allergic rhinitis after immunotherapy serum IL-10 levels are decreased but IFN-* no change.

Adult↗

PubMed1988

IgE and IgG antibody response to purified bee-venom antigens and peptides in four patients who had adverse reactions to immunotherapy.

The immunological response to individual bee-venom allergens was studied in blood samples collected at frequent intervals from four bee-venom allergic patients who had suffered systemic allergic reactions to injections of bee venom during immunotherapy. All had high IgE antibody levels, at the upper end of the range found in bee-sting allergic patients, and all had antibodies to the minor allergens at the time of the reactions. These did not, however, provide a simple explanation for the reactions that occurred. We were able to observe two interesting phenomena--in one patient IgE antibodies to the individual venom antigens appeared to be 'switched off' sequentially. In another, IgE antibodies to hyaluronidase rose substantially after 4 years of therapy. We believe that these results provide evidence to support the view that the regulation of IgE antibodies is controlled by mechanisms that are both isotype- and antigen-specific.

Acid Phosphatase↗

PubMedDate not supplied

Nonspecific changes in immunotherapy with house dust extract.

Despite the possible complications and inadequacies of the immunotherapy of allergic patients with house dust extracts (HDE), this is widely applied in Latin America and is commonly considered to be a cost-effective treatment for allergic diseases. Doubts about its efficacy and mechanism of action prompted us to evaluate the immunological changes that occurred in a group of 99 patients selected for their confirmed allergic sensitivity to house dust, and who showed significant clinical improvement after a minimum of 12 months of immunotherapy with HDE. The favorable clinical response of these patients was associated with some of the mechanisms reported for immunotherapy with pollen or venom allergens, such as increased levels of IgG or IgG4 "blocking" antibodies, and the increased affinity of these antibodies for house dust antigens, or diminished basophil sensitivity to HDE. However, the magnitude of these changes was relatively small, and their biological significance questionable. In contrast, particularly evident was a reduction in the cutaneous reactivity not only to the specific allergen, but also to the nonspecific mast cell degranulator codeine and to histamine. These results suggest that as yet unidentified "nonspecific" mechanisms might contribute to the effect of immunotherapy with extracts as heterogeneous and complex as HDE.

Adolescent↗