Immunoprophylaxis of atopy: light at the end of the tunnel?

doi:10.1016/0167-5699(94)90194-5

Immunology Today

Volume 15, Issue 10, October 1994, Pages 484-489

Immunology Today

https://doi.org/10.1016/0167-5699(94)90194-5 Get rights and content

Abstract

Current research in the field of atopy is directed almost exclusively towards treatment of established allergic disease. In particular, treatment has concentrated on controlling the release and actions of various mediators, such as cytokines, from the allergy effector cells at the end of the immunoinflammatory cascade. Here, Patrick Holt argues that a potentially more-effective and achievable goal may be the prevention of initial T helper 2 (Th2)-cell sensitization to environmental allergens during infancy. This might be achieved via amplification of the endogenous ‘immune deviation’ mechanism(s) that normally facilitate discrimination between pathogenic and non-pathogenic antigens at the mucosal surfaces of the body.

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Molecular diagnosis for allergen immunotherapy
2019, Journal of Allergy and Clinical Immunology
Citation Excerpt :
The schedule, administration route, and preparations that can be used for AIP (ie, to prevent the onset of allergic inflammation and the onset of symptoms) might be quite different (shorter or less invasive) than those used to suppress an already established allergic inflammation and the corresponding symptoms.39 Patrick Holt's proposal of “immunoprophylaxis of atopy” can today be expanded from a “primary” prevention concept for nonsensitized patients89,90 to a “secondary” AIP for patients (mainly children) already sensitized to grass pollen but still healthy.91 The Preventive Allergy Treatment (PAT) study proved the disease-modifying potential of AIT when applied early enough.92
The extensive use of allergen molecules in birth cohort studies revealed that atopic sensitization is a sequential IgE response to distinct non–cross-reacting molecules from the same allergenic source (ie, molecular spreading), starting with an initiator molecule. This phenomenon reaches different degrees of progression (monomolecular, oligomolecular, and polymolecular) according to the individual atopic propensity and allergen exposure, thus producing an extreme heterogeneity of IgE sensitization profiles in patient populations. In patients with allergic rhinitis, the broader the IgE molecular sensitization profile, the greater is the risk of asthma and other allergic comorbidities, such as oral allergy syndrome. Hence it has been proposed to anticipate immunologic intervention at disease onset (early allergen immunotherapy) or even earlier during the preclinical sensitization stage (allergen immunoprophylaxis). Diagnostic algorithms based on singleplex or multiplex molecular IgE tests allow the discrimination of genuine from cross-reacting sensitization and the selection of the right extracts for allergen immunotherapy composition. Patients with extreme molecular poly-sensitization and greater risk of asthma or other IgE-mediated comorbidities, can be easily identified by means of allergen microarray or macroarray procedures and might benefit from anti-IgE treatment. IgE molecular tests have opened the era of precision allergology, and their routine use should aim at cost-effectiveness, according to the principles of the Choosing Wisely initiative.
Clinical efficacy and safety of preseasonal sublingual immunotherapy with grass pollen carbamylated allergoid in rhinitic patients. A double-blind, placebo-controlled study
2006, Allergologia et Immunopathologia
The aim of this study was to confirm the clinical efficacy and safety of a preseasonal sublingual immunotherapy (SLIT) in a group of allergic patients with seasonal rhinoconjunctivitis with or without mild intermittent or mild persistent asthma. The immunotherapy was administered through the oral mucosa with a monomeric carbamylated allergoid (allergoid SLIT) for grass pollens. A secondary endpoint was to evaluate the effect of the allergoid SLIT on nasal reactivity.
A single-center, randomized, double-blind, placebo-controlled study was performed.Patients were selected and randomly allocatedto two groups: one group received active treatment (allergoid SLIT) for 2 years and the otherreceived placebo. Both groups received the necessary drug treatment throughout the trial. Thirty-three outpatients (20 men and 13 women, mean age: 30 years; range: 19-43) attending our center were enrolled in the study. Symptoms and medications were scored on diary cards during the pollen season. An allergen nasal challenge was performed at baseline and after 2 years of SLIT to evaluate nasal reactivity. Because the clinical scores were non-normally distributed, the Mann-Whitney and the Chi-square tests for intergroup comparisons and the Wilcoxon test for intragroup comparisons were used.
The results were evaluated after 1 and 2 years of treatment. Between the first and second years of treatment, no changes in the scores for the placebo group were found, while for the active vaccine group significant decreases were found in rhinorrhea (p < 0.03), sneezing (p < 0.03), and conjunctivitis (p < 0.02). Symptom scores after nasal challenge decreased (p < 0.03) after 2 years’ treatment. Nasal steroid use significantly decreased in the active treatment group during May and June in both the years of treatment (p < 0.02). Only two mild local adverse events were reported in the active group and none was reported in the placebo group.
The results of this study show thatthe allergoid SLIT is safe and effective in decreasing symptom scores and drug use in rhinitic patients allergic to grass pollen.
Development of sensitisation or tolerance following repeated OVA inhalation in BALB/cJ mice. Dose-dependency and modulation by the Al(OH)<inf>3</inf> adjuvant
2003, Toxicology
Anthropogenically induced exposures may, due to their adjuvant effect, promote development of sensitisation to commonly occurring aeroallergens. No generally accepted model exists for determination of adjuvant effect of airborne substances. Therefore, BALB/cJ mice were exposed for 10 consecutive days with ovalbumin (OVA) solution, 25 mg/l–10 g/l (0.0025–1%) for 20 min/day, with and without the Al(OH)₃ adjuvant (0.5%). Four days after the last aerosol exposure, no OVA specific IgE and only low IgG1 were produced. Subsequent parenteral OVA administration showed that the 10 g/l solution induced full tolerance of the IgE response, whereas only partial tolerance was apparent with 25 mg/l OVA. The Al(OH)₃ adjuvant counteracted development of tolerance that was fully prevented at the 25 mg/l OVA concentration. Development of IgG1 was increased in a concentration-dependent manner with 500 mg/l–10 g/l OVA. No increase occurred at the 25 mg/l level, but addition of Al(OH)₃ increased IgG1 production to the same level as the higher OVA concentrations. Concentrations from 1.25 mg/l to 10 g/l OVA were studied with ten exposures followed by once-weekly aerosol exposure for uptil 6 weeks. In the range from 1.25 mg/l to 10 g/l, IgE production was time- and concentration-dependent. Both the IgE and IgG1 production were markedly promoted by Al(OH)₃. However, with aerosol exposures, the IgE antibody productions were not sufficient to increase the level of inflammatory cells in broncho-alveolar lavage fluid. Overall, this study showed that airborne Al(OH)₃ was able to counteract tolerance and increase specific IgE and IgG1 production.
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2020, The Fundamentals of Hypersensitivities and Allergies
Therapy of Allergies and Allergy Immunotherapy in Children
2020, Laryngo- Rhino- Otologie
Joint effects of microbiological and environmental factors on ocular health and host defenses
2018, Microbiological Environmental Hygiene

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Immunology Today

Abstract

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Cited by (145)

Molecular diagnosis for allergen immunotherapy

Clinical efficacy and safety of preseasonal sublingual immunotherapy with grass pollen carbamylated allergoid in rhinitic patients. A double-blind, placebo-controlled study

Development of sensitisation or tolerance following repeated OVA inhalation in BALB/cJ mice. Dose-dependency and modulation by the Al(OH)<inf>3</inf> adjuvant

GELL AND COOMB’S CLASSIFICATION OF HYPERSENSITIVITY

Therapy of Allergies and Allergy Immunotherapy in Children

Joint effects of microbiological and environmental factors on ocular health and host defenses

ReviewImmunoprophylaxis of atopy: light at the end of the tunnel?

Abstract

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Review
Immunoprophylaxis of atopy: light at the end of the tunnel?