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  • 2005-2009  (3)
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  • 1
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Allergen-specific immunotherapy for food allergy has been hindered by severe side-effects in the past. Well-characterized hypo-allergenic recombinant food allergens potentially offer a safe solution.Objective To demonstrate hypo-allergenicity of a mutated major food allergen from apple, Mal d 1, in vitro and in vivo.Methods A mutant of the major apple allergen, Mal d 1, was obtained by site-directed mutagenesis exchanging five amino acid residues. Fourteen patients with combined birch pollen-related apple allergy were included in the study. Hypo-allergenicity of the mutant rMal d 1 (rMal d 1mut) compared with rMal d 1 was assessed by in vitro methods, i.e. RAST (inhibition), immunoblotting and basophil histamine release (BHR) and in vivo by skin prick test and double-blind placebo-controlled food challenge (DBPCFC).Results RAST analysis (n=14) revealed that IgE reactivity to rMal d 1mut was twofold lower than that of the wild-type molecule (95% confidence interval (CI): 1.7–2.4). RAST inhibition (n=6) showed a 7.8-fold decrease in IgE-binding potency (95% CI: 3.0–12.6). In contrast to this moderate decrease in IgE-binding potency, the biological activity of rMal d 1mut assessed by SPT and BHR decreased 10–200-fold. Hypo-allergenicity was confirmed by DBPCFC (n=2) with both recombinant molecules.Conclusion A moderate decrease in IgE-binding potency translates into a potent inhibition of biological activity. This is the first study that confirms by DBPCFC that a mutated recombinant major food allergen is clinically hypo-allergenic. This paves the way towards safer immunotherapy for the treatment of food-allergic patients.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Environmental control has been put forward as an integral part of the management of house dust mite (HDM) allergy in sensitized patients. To validate this statement allergic disorders involved in HDM allergy – allergic asthma, rhinitis and atopic eczema/dermatitis syndrome (AEDS) – should be taken together and studied in terms of the efficacy of environmental control. Because a generic quality of life questionnaire exceeds the border of disease, this may be used as major outcome parameter.Research objective:  To study the effects of bedding encasings in HDM allergic patients with asthma, rhinitis and AEDS.Material and methods:  A total of 224 adult HDM allergic patients with rhinitis and/or asthma and/or dermatitis were randomly allocated impermeable or nonimpermeable encasings for mattress, pillow and duvet. Short form 36 (SF-36) was filled in at baseline and after 12 months.Results:  Lower physical (P = 0.01) and emotional (P 〈 0.001) sumscores were seen in females. Also, the presence of asthma resulted in lower physical sumscore (P = 0.01). However, no effect was seen of encasings on either sumscore.Conclusion:  Bedding encasings do not improve quality of life in a mixed population of subjects with combinations with rhinitis, asthma and atopic dermatitis and sensitized to HDMs.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Eosinophils may play an important role in the pathogenesis of atopic dermatitis (AD). Interleukin-5 is essential for eosinophil growth, differentiation and migration. A monoclonal antibody to human interleukin-5 (mepolizumab) was developed for atopic diseases. This study was designed to study the effect of mepolizumab in AD.Methods:  Two single doses of 750 mg mepolizumab, given 1 week apart, were studied in patients with moderate to severe AD using a randomized, placebo-controlled parallel group design. The primary endpoint of ‘success’ to treatment was defined as the percentage of patients with at least ‘marked improvement’ after 2 weeks as assessed by the Physician's Global Assessment of Improvement (PGA). Furthermore, SCORing AD (SCORAD), pruritus scoring, number of blood eosinophils and serum thymus and activation-regulated chemokine (TARC) values served as secondary endpoints. Fluticason propionate cream 0.05%, once daily could be used as rescue medication from day 16 if no improvement was recorded.Results:  Eighteen patients received mepolizumab and 22 placebo treatment. Peripheral blood eosinophil numbers were significantly reduced in the treatment group compared with placebo (P 〈 0.05). No clinical success was reached by PGA assessment (P = 0.115), SCORAD (P = 0.293), pruritus scoring and TARC values in the mepolizumab-treated group compared with placebo. However, modest improvement (〈50% improvement) assessed by PGA was scored significantly more in the mepolizumab-treated group compared with placebo (P 〈 0.05).Conclusion:  Two single doses of 750 mg mepolizumab did not result in clinical success in patients with AD, despite a significant decrease in peripheral blood eosinophils.
    Type of Medium: Electronic Resource
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