Immunotherapy with cat- and dog-dander extracts II. In vivo and in vitro immunologic effects observed in a 1-year double-blind placebo study

Hedlin, Gunilla; Graff‐Lonnevig, V.; Heilborn, H.; Lilja, G.; Norrlind, K.; Pegelow, Kjell-Orvar; Sundin, Bo; Løwenstein, Henning

doi:10.1016/0091-6749(86)90184-3

Cited by 92 publications

(43 citation statements)

References 38 publications

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“…The changes in IgG4 concentrations observed here in a clinically effective treatment regimen were statistically significant but modest compared to those reported in some immunotherapy studies (1.4- to 2.8-fold). This most likely relates to the allergen dose used, as a dose-response effect has been reported, and the changes we detected were similar to those seen for other immunotherapy regimens such as for Alternaria [24], cat [25] or house dust mite [26]. Notably, not all patients showed an increase in allergen-specific IgG4 after immunotherapy with Dpg-Pol extract at this dose.…”

Section: Discussionmentioning

confidence: 61%

Depigmented and Polymerised House Dust Mite Allergoid: Allergen Content, Induction of IgG4 and Clinical Response

Gallego

Iraola

Himly

et al. 2010

Int Arch Allergy Immunol

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Background: Polymerised allergenic extracts (allergoids) are commonly used in allergen immunotherapy. Clinical efficacy and safety of these extracts have been demonstrated. Recently, allergen sequences have been identified by mass spectrometry in depigmented and polymerised (Dpg-Pol) extracts. The objectives of this study were to investigate the presence of allergens in Dpg-Pol extracts of house dust mite and to analyze the immunological changes induced by these extracts in asthmatic patients enrolled in a double-blind, placebo-controlled study. Methods: Dpg-Pol extracts were manufactured and vaccines with a composition of 50% Dermatophagoides pteronyssinus and 50% D. farinae (100 HEPL/ml) were prepared. Allergen composition was analyzed by mass spectrometry. Patients with asthma and rhinoconjunctivitis were treated in a 1-year, double-blind, placebo-controlled, parallel-group study with 6 up-dosing and monthly maintenance injections. Specific IgE and IgG4 titres to D. pteronyssinus, Der p 1 and Der p 2 were measured in patients’ sera using the CAP system and direct ELISA experiments. Results: Sequences from the major allergens Der p 1 and Der p 2 and from other allergens were identified in native and Dpg-Pol extracts. There was a statistically significant increase in specific IgG4, a decrease in the ratio of IgE/IgG4 to D. pteronyssinus and a significant increase in specific IgG4 to Der p 1 and Der p 2 in the patients allotted to active treatment. Conclusions: The detection of allergen sequences suggests preservation of major and minor allergens in Dpg-Pol allergoids from house dust mites. Efficacy in asthma treatment and the increase in specific IgG4 seem to be associated with the presence of major allergens in Dpg-Pol allergen extracts.

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Section: Discussionmentioning

confidence: 61%

Depigmented and Polymerised House Dust Mite Allergoid: Allergen Content, Induction of IgG4 and Clinical Response

Gallego

Iraola

Himly

et al. 2010

Int Arch Allergy Immunol

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“…1,2 Drugs that are used to treat allergies, such as antihistamines or corticosteroids, ameliorate symptoms but do not stop progression; the only therapy that modifies progression of allergies is allergen-specific immunotherapy (SIT). SIT has major disadvantages, however, in that it requires numerous allergen administrations over 3 to 5 years 3,4 and can cause severe adverse events that range from local allergic reactions to anaphylaxis. 5 SIT has been reported to modify different aspects of the immune system, inducing a shift of allergy-promoting T H 2 cells to T H 1 cells, 6 epitope-specific T-cell anergy, 7 and allergen-specific regulatory T cells that suppress the responses of effector T cells.…”

mentioning

confidence: 99%

Mechanisms of allergen-specific desensitization

Uermösi¹,

Beerli²,

Bauer³

et al. 2010

Journal of Allergy and Clinical Immunology

109

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SUMMARY SUMMARYProtective immunity is provided by the interplay between the innate and the adaptive arms of the immune systems. The innate as well as the adaptive immune response is regulated by specialized cells with the challenging task to eliminate pathogens while not damaging the host itself. Usually the immune system copes well with this charge, but is not always successful. Furthermore, proinflammatory lipids, cytokines, and chemokines are produced and released, leading to an allergic inflammation. Although frequency of individuals suffering from allergies has increased exponentially over the last century, the only available therapy that stops disease progression is allergen-specific immunotherapy (SIT). Even though allergenspecific antibodies have been reported to play an important role in SIT, mechanisms of IgGmediated inhibition of allergic reactions are not well defined.The present studies aimed to provide better understanding of the mechanisms how allergenspecific IgG antibodies may modulate allergic responses. Therefore, we generated monoclonal antibodies (mAbs) that recognize three non-overlapping epitopes on the major cat allergen Feld1. Each of the three mAbs was produced as IgE or different IgG isotypes. We found that IgE antibodies against two non-overlapping epitopes on Feld1 were required and sufficient to sensitize mast cells for maximal activation upon exposure to monomeric Feld1.

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“…It was previously thought that loss of a seasonal rise in serum IgE antibody levels and/or the formation of IgGblocking antibodies mediated hyposensitization of various allergic diseases [3][4][5]. Although a significant overall association between changes of antibody levels after hyposensitization and clinical effects has been found, there are always a considerable number of exceptions [6,7]. Meanwhile, in vitro studies revealed that T-lymphocyte anergy could be the main system of hyposensitization [8][9][10], indicating the possibility that modulated functions of T lymphocytes are involved in the mechanism of hyposensitization.…”

Section: Introductionmentioning

confidence: 90%

“…Regarding the humoral immune response, suppression of IgE production was demonstrated in patients with hay fever [30] and in mice treated with modified allergens [23]. Increased levels of IgG-blocking antibody have been demonstrated in patients with bronchial asthma [6], hay fever [7], and perennial rhinitis [5]. However, changes in the levels of these antibodies do not seem to fully account for the suppression of symptoms [6,7].…”

Section: Oa-specific Ige Levelsmentioning

confidence: 99%

“…Increased levels of IgG-blocking antibody have been demonstrated in patients with bronchial asthma [6], hay fever [7], and perennial rhinitis [5]. However, changes in the levels of these antibodies do not seem to fully account for the suppression of symptoms [6,7]. The observation that the loss of antigen-induced bronchial response was not associated with any changes in serum antigen-specific IgE levels in our animal model is consistent with findings in humans and suggests that immune phenomena other than humoral responses are also important in the mechanism of hyposensitization.…”

Section: Oa-specific Ige Levelsmentioning

confidence: 99%

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Hyposensitization Attenuates Airway Inflammation and Antigen-Induced Proliferative Response by Lymphocytes in a Rat Model of Bronchial Asthma

Ohnuma

Yamaguchi²,

Oguri³

et al. 1998

Respiration

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The mechanism of hyposensitization in bronchial asthma has not been fully elucidated. We established a hyposensitization model of bronchial asthma in rats and examined airway responses and immunological parameters. Brown Norway rats were sensitized by a subcutaneous injection of ovalbumin (OA) at day 1 and by the inhalation of 2% OA aerosol at day 15. Animals were hyposensitized by intraperitoneal injections of OA from day 17 to day 22. They were challenged with OA or acethylcholine (Ach) aerosol at day 23 and changes in intratracheal pressure were recorded. Lungs were lavaged and OA-induced proliferative responses by blood lymphocytes were examined for animals without aerosol challenge at day 23. OA-specific serum IgE levels were measured by enzyme-linked immunosorbent assay. Hyposensitization significantly reduced the OA-induced immediate airway response, accumulation of CD4+ lymphocytes and eosinophils recovered by bronchoalveolar lavage, and the OA-induced proliferative response by blood lymphocytes. The airway responses to Ach and serum OA-specific IgE levels in hyposensitized group were not significantly different from those in the sensitized group. These results indicate that amelioration of airway inflammation and hyporesponsiveness of lymphocytes against OA are involved in the attenuated immediate antigen-induced airway response following hyposensitization.

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Immunotherapy with cat- and dog-dander extracts II. In vivo and in vitro immunologic effects observed in a 1-year double-blind placebo study

Cited by 92 publications

References 38 publications

Depigmented and Polymerised House Dust Mite Allergoid: Allergen Content, Induction of IgG4 and Clinical Response

Depigmented and Polymerised House Dust Mite Allergoid: Allergen Content, Induction of IgG4 and Clinical Response

Mechanisms of allergen-specific desensitization

Hyposensitization Attenuates Airway Inflammation and Antigen-Induced Proliferative Response by Lymphocytes in a Rat Model of Bronchial Asthma

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