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[Pharmacotherapy of immune diseases].
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[Hyposensitization: action and immunological procedure].
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[A national survey: the respiratory specialist and allergology].
In June 1984 we wrote to all 1,594 Registered French Respiratory Specialists in the medical directory, with a questionnaire to determine their diagnostic and therapeutic activity in the field of allergy. In September 1984 a second letter with the same questionnaire was sent to these Physicians who had not replied to the first. Finally in October 1984 a random sample of 21 Physicians who had not replied to the two letters were contacted by telephone. Among the 1,594 letters initially, 232 were to people not involved in the field of inquiry (Deceased doctors, those retired or not thoracic Physicians) or had not reached the address. After excluding this group, the level of response was established at 74% for the first delivery and 33% for second or 84% overall. Among 1,114 respondents overall, 79% admitted to activity in allergy varying from 55% in the Paris Region to a maximum of 92% in the South-East. The differences were less pronounced when the age of the physicians was allowed for. The most used diagnostic means are skin tests (90%), total IgE (68.6%) and specific IgE (57%) far ahead of non-specific bronchial provocation tests (20%) and specific tests (14.6%). Two hundred and sixty thoracic Physicians had no activity in the field of allergy.
The pathogenesis of the immunologic granuloma.
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Specific immunotherapy in pollinosis: II. Forecasting changes in certain cytoimmunological indicators after four years of immunotherapy in pollinosis.
The determination of an appropriate period of duration for specific immunotherapy presents an important problem in the treatment of allergic diseases. The aim of this paper was to conduct a prognostic study of certain immunological indicators after 4 years of desensitization, and to determine which of the tested indicators are characteristic for an evaluation of the clinical condition. Individuals with pollinosis were tested after the first, second, third and fourth year of desensitization using the pollen allergen. The B and T-lymphocyte counts, the levels of immunoglobulins A, M, G, and total and specific E, and the volume of basal, total and specifically released histamine were all measured. Furthermore, the clinical condition of the patient was defined using a score method (0-3 points), taking into account the results of testing and the basic symptoms of the disease. Following this, a prediction of results after the fifth year of desensitization was made, using Brown's method of exponential smoothing. The majority of the data obtained from the forecasting study indicate that in the subsequent fifth year of desensitization, the indicators studied should undergo further changes in values, offering a strong argument for the necessity of extending the period of immunotherapy in pollinosis beyond three years. In the results of the regression function estimates it was determined that, among the indicators studied, those which are helpful in monitoring treatment are: T-RFC, T-FcG-BG, T-FcM-EN and B-EAC lymphocyte counts, levels of IgA, IgM and specific IgE, and the percentage of specifically released histamine.
Local nasal immunotherapy. Proceedings of a satellite symposium to the XVI Congress of European Academy of Allergology and Clinical Immunology. Madrid, June 1995.
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The position of immunotherapy in the European Academy of Allergology and Clinical Immunology.
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A circulating suppressive factor of platelet cytotoxic functions after rush immunotherapy in Hymenoptera venom hypersensitivity.
A receptor for the Fc fragment of IgE has been described on human blood platelets. This receptor mediated the IgE-dependent stimulation of platelets by the specific allergen in Hymenoptera venom (HV) hypersensitivity. This platelet reactivity was abolished after rush desensitization. To understand the mechanism of such a down-regulation, we studied the effects of sera recovered from patients treated by HV rush desensitization on platelets of untreated HV sensitive patients. The present data describe the presence of a circulating factor able to suppress, in a dose-dependent manner, platelet stimulation by the specific allergen. This circulating factor was not allergen specific, not depleted by IgE or IgG antibody immunoadsorption, and was found at higher concentrations in the sera of patients receiving monthly high dosages of HV (200 micrograms maintenance dose). The physicochemical characterization showed that this circulating factor had a m.w. of 20,000 to 25,000, an isoelectric point of 4.2, was heat and acid stable, and sensitive to trypsin, but not to neuraminidase. These characteristics were similar to a newly described lymphokine, platelet activity suppressive lymphokine, suggesting the intervention of such a lymphokine in HV rush desensitization.
Rate of desensitization to HL-A antibodies in phytohaemagglutinin (PHA) stimulated lymphocytes.
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[Immunologic studies of the serum of patients with infectious hepatitis by means of anaphylaxis with subsequent desensitization].
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Allergen immunotherapy for asthma.
BACKGROUND: Allergen specific immunotherapy has long been a controversial treatment for asthma. Although beneficial effects upon clinically relevant outcomes have been demonstrated in randomised controlled trials, there remains a risk of severe and sometimes fatal anaphylaxis. The recommendations of professional bodies have ranged from cautious acceptance to outright dismissal. With increasing interest in new allergen preparations and new methods of delivery, it was time to conduct a systematic review of allergen specific immunotherapy for asthma. OBJECTIVES: Allergen specific immunotherapy involves injecting an extract of the allergen under the skin. It is also known as hyposensitisation or desensitisation, and carries a risk of potentially fatal anaphylaxis. The objective of this review was to assess the effects of allergen specific immunotherapy for asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register up to 1997, Dissertation Abstracts, WorldCat and ArticleFirst. SELECTION CRITERIA: Randomised trials using various forms of allergen specific immunotherapy to treat asthma. DATA COLLECTION AND ANALYSIS: Eligibility of studies for inclusion was decided by three reviewers independently. Quality assessment of studies was performed by two reviewers independently. MAIN RESULTS: Fifty-four trials were included. There were 25 trials of immunotherapy for house mite allergy; 13 pollen allergy trials; eight animal dander allergy trials; two Cladosporium mould allergy and six trials looking at multiple allergens. Concealment of allocation was assessed as clearly adequate in only 11 of these trials. Significant heterogeneity was present in a number of comparisons. Overall, there was a significant reduction in asthma symptoms and medication following immunotherapy. There was also a significant improvement in asthma symptom scores (standardised mean difference -0.52, 95% confidence interval -0.70 to -0.35). People receiving immunotherapy were less likely to report a worsening of asthma symptoms than those randomised to placebo (odds ratio 0.27, 95% confidence interval 0.21 to 0.35). People randomised to immunotherapy were less likely to require medication than those randomised to placebo (odds ratio 0.28, 95% confidence interval 0.19 to 0.42). Allergen immunotherapy reduced allergen specific bronchial hyper-reactivity, with some reduction in non-specific bronchial hyper-reactivity as well. There was no consistent effect on lung function. REVIEWER'S CONCLUSIONS: Immunotherapy may reduce asthma symptoms and use of asthma medications, but the size of the benefit compared to other therapies is not known. The possibility of adverse effects (such as anaphylaxis) must be considered.
Lymphocyte-mediated inhibition of platelet cytotoxic functions during Hymenoptera venom desensitization: characterization of a suppressive lymphokine.
Recently, it has been shown that platelets, through a receptor for the Fc fragment of IgE, could be specially triggered by venom allergens in hypersensitivity to hymenoptera, generating cytocidal mediators toward Schistosoma mansoni larvae, and oxygen metabolites measured by chemiluminescence. After rush immunotherapy, a depressed platelet response was demonstrated to be associated with the production of lymphokine(s). Here we report the characterization of a factor present in supernatants of antigen-stimulated T cells from patients after hymenoptera venom desensitization which is able to inhibit platelet cytotoxic functions in a dose-dependent manner. The optimal inhibition was observed with supernatants obtained after T lymphocyte stimulated with 10(-5) micrograms venom allergen/ml. Once specifically produced the platelet-suppressive effect of lymphocyte supernatants was not antigen specific. The producing T cell subpopulation was identified as CD8+. This lymphokine had an approximate molecular mass of 25 kDa and a pI of 4.8. It was heat and acid stable and sensitive to trypsin and proteinase K but not to neuraminidase. This platelet inhibitory activity was absorbed by platelet membrane suggesting its binding to a receptor. These properties were very similar to a previously described platelet activity suppressive lymphokine, suggesting the participation of this lymphokine in the mechanisms of rush desensitization.
Decrease of IgE-dependent platelet activation in Hymenoptera hypersensitivity after specific rush desensitization.
A receptor for the Fc fragment of IgE on human platelets has been recently described, which mediated an IgE-dependent activation in the presence of specific allergen. We investigated the allergen-induced activation of platelets from patients with Hymenoptera hypersensitivity before and after specific rush desensitization. Nineteen patients with a history of anaphylactic reactions were included (15 sensitive to yellow-jacket and four to honey-bee venom), fourteen/nineteen having experienced severe life-threatening systemic reactions and 5/19 large local reactions. All showed positive skin tests and high values of specific IgE. By comparison to the baseline results obtained before desensitization, a significant decrease of platelet activation (76.8% inhibition) after rush desensitization was observed. In the case of two polysensitized patients, after Hymenoptera venom desensitization alone, platelets not only lost their reactivity to venom but also towards the other allergen. This modulation of the IgE-dependent platelet reactivity during desensitization offers therefore a new approach for the study of allergen-induced desensitization.
Oral desensitizing treatment in food allergy: clinical and immunological results.
BACKGROUND: The possibility of inducing oral desensitization in patients with food allergy is still controversial and no standardized programmes are yet available. AIM: To evaluate the safety and efficacy of oral desensitization in patients with allergy induced by the most common food allergens. METHODS: Fifty-nine patients with food allergy underwent an oral desensitizing treatment according to standardized protocols. The control group consisted of age- and sex-matched subjects, who followed a strict elimination diet. Specific immunoglobulin E and immunoglobulin G4 were assessed at baseline and after 6, 12 and 18 months. RESULTS: The majority of patients (83.3%) successfully completed the treatment. During treatment, 51.1% of subjects experienced some mild side-effects, easily controlled by the oral administration of antihistamines or sodium cromolyn. Specific immunoglobulin E showed a significant decrease, whilst specific immunoglobulin G4 showed a significant increase in all patients. CONCLUSIONS: The immunological findings induced by oral desensitization in food allergy allow us to hypothesize that oral tolerance may be mediated by the same mechanisms as those involved in traditional desensitizing treatments for respiratory allergies. Moreover, the proposed standardized oral desensitization protocols may represent an effective alternative approach in the management of food-allergic patients.
Desensitized renal transplant recipients show reduced cellular responses to in vitro challenge.
Intravenous immunoglobulin (IVIG) desensitization protocols permit transplantation of sensitized renal recipients against alloantibody incompatibility barriers. It appears that IVIG induces a sustained down-regulation of alloantibody that facilitates crossmatch compatibility. However, the consequence of desensitization upon cellular immunity has not been addressed. We compared in vitro proliferative responses and cytokine expression between desensitized transplant recipients (IVIG) and non-IVIG-treated patients (controls). Eleven patients who were crossmatch-incompatible with living donors underwent treatment with IVIG and plasmapheresis. Nine patients converted to negative crossmatches and were transplanted. With a mean follow-up time of 17.6 +/- 6.7 months, graft survival is 100%. Peripheral mononuclear cells were collected 12.5 +/- 9 months after transplantation and tested for proliferative response and cytokine elaboration following challenge with staphylococcal enterotoxin b (SEB) and donor-specific mixed lymphocyte reaction (dMLR). Proliferative reactions were 90% lower (P < .05) among IVIG versus controls in response to SEB and dMLR challenge. Cytokine response to SEB challenge was equivalent (P = NS) between IVIG and controls. In contrast, cytokine elaboration was 60% lower (P < .05) for IVIG versus controls in response to dMLR. One year after renal transplantation, desensitized patients showed in vitro hyporesponsiveness to superantigen and donor-specific challenge. This suggests that IVIG promotes a down-regulation in cellular immunity that may facilitate good graft outcome.
BRIDGING THE GAP BETWEEN IMMUNOLOGY AND ALLERGY IN PEDIATRIC PRACTICE.
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Insulin allergy.
While immunologic responses to insulin such as cutaneous reactivity and antibody against insulin are common significant clinical problems related to those immunologic reactions are uncommon. Immunologic responses that have been described included Gell and Coombs type I, II, and IV. The antigen may be the result of any of several factors: insulin as a heterologous protein, altered tertiary structure of insulin, presence of non-insulin protein contaminants, or pharmaceutical formulation additives. IgE mediated local reactions are the most common and almost always subside spontaneously. IgE mediated anaphylaxis is the most important immunologic problem; it can be managed safely and successfully by temporary reduction in dose or by insulin desensitization. Other systemic immunologic reactions, insulin resistance and serum sickness, are extremely rare and respond to corticosteroid therapy.