[Show abstract][Hide abstract] ABSTRACT: During recent years, much research has been conducted on oral and sublingual immunotherapy in food allergy. Although efficacy has been shown for this treatment in terms of desensitization, long-term efficacy with regard to tolerance development is not yet proven. More importantly, safety remains a major issue. Although immunotherapy is already performed routinely in some countries, we currently do not recommend this therapeutic approach outside clinical trials. There have been only five randomized placebo-controlled trials but more than 34 reviews on oral immunotherapy in food allergy, indicating that more research is needed. Therefore, the current option for patients with food allergy remains avoidance of the offending food, and because of the constant risk of accidental exposure, patients are advised to use auto-injectable epinephrine in the case of anaphylactic reactions.
[Show abstract][Hide abstract] ABSTRACT: Threshold levels for peanut allergy determined by using oral challenges are important for the food industry with regard to allergen labeling. Moreover, the utility of biological markers in predicting threshold levels is uncertain.
We sought to use a modified oral food challenge regimen that might determine threshold levels for peanut allergy mimicking a more real-life exposure and to correlate the eliciting dose (ED) and severity of clinical reaction in children with peanut allergy with B-cell, T-cell, and effector cell markers.
A modified food challenge procedure with doses scheduled 2 hours apart was used in 63 children with peanut allergy. All children received a maximum of 8 semi-log increasing titration steps of roasted peanuts ranging from 3 to 4500 mg of peanut protein until objective allergic reactions occurred. Severity of symptoms was graded from I to V. Biological markers were measured before challenge.
Forty-five of 63 patients showed objective symptoms after greater than 30 minutes, with a median latency of clinical reaction of 55 minutes. By using a log-normal dose-distribution model, the ED5 was calculated to be 1.95 mg of peanut protein. The ED was significantly and inversely correlated with peanut- and Ara h 2-specific IgE levels, skin prick test responses, basophil activation, and TH2 cytokine production by PBMCs. Symptom severity did not correlate with any of the markers or the ED.
This modified food challenge procedure might better reflect threshold levels for peanut allergy than the standard procedure because most of the patients reacted at a time interval of greater than 30 minutes. By using this model, threshold levels, but not severity, could be correlated with biological markers.
The Journal of allergy and clinical immunology 05/2014; 134(2). DOI:10.1016/j.jaci.2014.03.035 · 11.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ten years ago, avoidance measures such as the performance of latex-free operations were implemented in children with spina bifida. Since then, latex sensitization and latex allergy have decreased in this high-risk group.
To study the effect of primary latex-free prophylaxis on the prevalence of allergic diseases and atopy as a marker for sensitization spreading in children with spina bifida.
One hundred and twenty children with spina bifida born after the introduction of latex-free prophylaxis and operated on under latex-free conditions ('current group') were examined for latex sensitization, latex allergy, sensitization to aero- and food allergens and allergic diseases. Results were compared to a 'historic' (not latex-free operated) group of children with spina bifida and comparable age (n = 87) and to a recent sample of children from the general population (n = 12,403).
In comparison with the 'historic group', latex sensitization (55% vs 5%, P < 0.001) and latex allergy (37% vs 0.8%, P < 0.001) were significantly reduced in the 'current group'. Furthermore, a significant reduction could be demonstrated for sensitization to aeroallergens (41.4% vs 20.8%, P = 0.001) and for allergic diseases (35% vs 15%, P = 0.001). The prevalence for atopy, sensitization to aero-/foodallergens and for allergic diseases in children of the 'current group' was similar to those in children of the weighted population sample.
Latex avoidance in children with spina bifida prevents latex sensitization and latex allergy. Additionally, it also seems to prevent sensitization to other allergens and allergic diseases which might be explained by the prevention of sensitization spreading.
[Show abstract][Hide abstract] ABSTRACT: The only treatment option for peanut allergy is strict avoidance.
To investigate efficacy and safety of oral immunotherapy (OIT) in peanut allergy.
Twenty-three children (age, 3.2-14.3 years) with IgE-mediated peanut allergy confirmed by positive double-blind, placebo-controlled food challenge (DBPCFC) received OIT following a rush protocol with roasted peanut for 7 days. If a protective dose of at least 0.5 g peanut was not achieved, patients continued with a long-term buildup protocol using biweekly dose increases up to at least 0.5 g peanut. A maintenance phase for 8 weeks was followed by 2 weeks of peanut avoidance and a final DBPCFC. Immunologic parameters were determined.
After OIT using the rush protocol, patients tolerated a median dose of only 0.15 g peanut. Twenty-two of 23 patients continued with the long-term protocol. After a median of 7 months, 14 patients reached the protective dose. At the final DBPCFC, patients tolerated a median of 1 g (range, 0.25-4 g) in comparison with 0.19 g peanut at the DBPCFC before OIT (range, 0.02-1 g). In 2.6% of 6137 total daily doses, mild to moderate side effects were observed; in 1.3%, symptoms of pulmonary obstruction were detected. OIT was discontinued in 4 of 22 patients because of adverse events. There was a significant increase in peanut-specific serum IgG(4) and a decrease in peanut-specific IL-5, IL-4, and IL-2 production by PBMCs after OIT.
Long-term OIT appears to be safe and of some benefit in many patients with peanut allergy. With an increase in threshold levels and a reduction of peanut-specific T(H)2 cytokine production, the induction of tolerance may be feasible in some patients.
The Journal of allergy and clinical immunology 07/2010; 126(1):83-91.e1. DOI:10.1016/j.jaci.2010.04.030 · 11.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Farming has been widely reported to be associated with decreased risk of developing atopic disorders, but underlying immunomodulatory mechanisms are still not fully defined. We delineated T-cell functions after induction of mucosal tolerance in the context of intranasally delivered organic dust compounds, lipopolysaccharides (LPS).
BALB/c mice were pretreated intranasally with ovalbumin (OVA) with or without LPS (Escherichia coli) three times (days -21, -14, -7) prior to systemic OVA sensitization (days 1 and 14) and airway allergen challenges (days 28-30). CD4+ spleen T cells from pretreated and sensitized donors were characterized for cytokine function, and transferred into naive recipients prior to subsequent OVA sensitization and challenges.
Intranasal OVA pretreatment suppressed Th2-mediated immune and inflammatory responses and enhanced frequency of regulatory T cells in OVA-sensitized and -challenged mice. Addition of LPS to OVA, but not LPS alone, inhibited development of allergen-induced sensitization and eosinophilic airway infiltration, and markedly enhanced allergen-specific IgG1 serum levels and frequencies of IL-10- and IFN-gamma-producing CD4+ T cells. Transfer of CD4+ spleen T cells from OVA-pretreated animals protected naive recipients against subsequent allergen sensitization and airway disease, whereas transfer from LPS/OVA-pretreated animals only protected against allergen sensitization.
Microbial LPS modulated mucosal tolerance by inducing allergen-specific IgG1 production and distinct effector CD4+ T cells with a mixed regulatory/Th1 phenotype. Organic dust components such as LPS might therefore be important immune modulators in naturally occurring or preventive allergen-specific tolerance induction.
International Archives of Allergy and Immunology 05/2008; 147(1):25-34. DOI:10.1159/000128583 · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: New preventive strategies against the development of allergic diseases focus on potentially immunomodulatory components, such as bacterial LPSs. Optimal time frames for initiating immunomodulation to receive a sufficient effect against allergen sensitization are still unclear.
Using a mouse model, we investigated the influence of prenatal LPS exposure on later allergen-mediated sensitization and airway inflammation in the offspring.
Pregnant BALB/c mice were repeatedly exposed to aerosolized LPS (LPS Escherichia coli; 3x per week, day 7 of gestation time up to delivery). Some of the offspring were further exposed to aerosolized LPS before allergen sensitization with ovalbumin (OVA; administered intraperitoneally day 28 up to day 42) and OVA airway challenges (days 56-58). Positive control animals were placebo exposed to PBS instead of LPS, and negative control animals were first placebo exposed and later placebo sensitized with PBS instead of OVA.
Compared with positive control animals, prenatal LPS exposure suppressed (1) allergen-specific sensitization (IgE production), (2) eosinophilic airway inflammation (reduced numbers of eosinophils in bronchoalveolar lavage fluids), and (3) in vivo airway reactivity in response to methacholine. These effects occurred only when prenatal was combined with further postnatal LPS exposure. Suppression of allergen-mediated inflammatory responses was associated with increased Toll-like receptor and T-bet expression by lung tissues and a shift toward predominantly T(H)1 immune responses in spleen cells cultured with OVA in vitro.
Prenatal initiated and postnatal sustained LPS exposure increased endotoxin susceptibility and prevented later allergen sensitization in offspring through inhibition of T(H)2 immune responses.
Immunomodulation with bacterial compounds during gestation time might be an effective mode for first-step primary prevention against allergic diseases.
Journal of Allergy and Clinical Immunology 10/2006; 118(3):666-73. DOI:10.1016/j.jaci.2006.05.022 · 11.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Spreading of sensitization with clinical manifestation of allergy is often observed in atopic individuals.
To investigate the effects of an established primary allergen sensitization on immune responses and airway inflammation/reactivity on secondary allergen sensitization and airway challenges in a murine model.
Balb/c mice were primarily sensitized intraperitoneally with ovalbumin or PBS, followed by systemic sensitization and airway challenges with latex extract as a secondary, unrelated allergen. Purely sham-sensitized animals were included as controls. In a second set of experiments, the primary and secondary allergens were switched.
Sensitization with ovalbumin before sensitization with latex resulted in increased production of total and latex-specific (Hev b 3-specific) IgE and IgG(1), and enhanced secretion of T(H)2-cytokines by spleen mononuclear cells cultured with mitogen compared with single latex-sensitized mice. Furthermore, airway challenges of double-sensitized mice (ovalbumin + latex) with latex caused a significant increase in airway reactivity compared with purely latex-sensitized and challenged animals. These effects were dependent on dosing and timing of the primary sensitization in relation to the secondary sensitization and independent of the primary allergen used.
Primary sensitization boosted systemic T(H)2 immune responses and enhanced the development of airway reactivity after sensitization and airway challenges with a secondary, unrelated allergen. This effect of consecutive priming was dependent on the strength of the primary sensitization but independent of the allergen used. The results explain the increased susceptibility toward sensitization spreading in atopic individuals.
Because sensitization spreading is facilitated by primary sensitization, early prevention measurements or immunotherapy should be considered at this stage of monosensitization.
Journal of Allergy and Clinical Immunology 10/2006; 118(3):615-21. DOI:10.1016/j.jaci.2006.04.054 · 11.48 Impact Factor