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A mutant of the major apple allergen, Mal d 1, demonstrating hypo-allergenicity in the target organ by double-blind placebo-controlled food challenge.
Clin Exp Allergy. 2005 Dec; 35(12):1638-44.CE

Abstract

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.

Authors+Show Affiliations

Department of Dermatology/Allergology, University Medical Center Utrecht, Utrecht, The Netherlands. s.bolhaar@azu.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16393331

Citation

Bolhaar, S T H P., et al. "A Mutant of the Major Apple Allergen, Mal D 1, Demonstrating Hypo-allergenicity in the Target Organ By Double-blind Placebo-controlled Food Challenge." Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, vol. 35, no. 12, 2005, pp. 1638-44.
Bolhaar ST, Zuidmeer L, Ma Y, et al. A mutant of the major apple allergen, Mal d 1, demonstrating hypo-allergenicity in the target organ by double-blind placebo-controlled food challenge. Clin Exp Allergy. 2005;35(12):1638-44.
Bolhaar, S. T., Zuidmeer, L., Ma, Y., Ferreira, F., Bruijnzeel-Koomen, C. A., Hoffmann-Sommergruber, K., van Ree, R., & Knulst, A. C. (2005). A mutant of the major apple allergen, Mal d 1, demonstrating hypo-allergenicity in the target organ by double-blind placebo-controlled food challenge. Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, 35(12), 1638-44.
Bolhaar ST, et al. A Mutant of the Major Apple Allergen, Mal D 1, Demonstrating Hypo-allergenicity in the Target Organ By Double-blind Placebo-controlled Food Challenge. Clin Exp Allergy. 2005;35(12):1638-44. PubMed PMID: 16393331.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A mutant of the major apple allergen, Mal d 1, demonstrating hypo-allergenicity in the target organ by double-blind placebo-controlled food challenge. AU - Bolhaar,S T H P, AU - Zuidmeer,L, AU - Ma,Y, AU - Ferreira,F, AU - Bruijnzeel-Koomen,C A F M, AU - Hoffmann-Sommergruber,K, AU - van Ree,R, AU - Knulst,A C, PY - 2006/1/6/pubmed PY - 2006/5/5/medline PY - 2006/1/6/entrez SP - 1638 EP - 44 JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JO - Clin Exp Allergy VL - 35 IS - 12 N2 - 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. SN - 0954-7894 UR - https://www.unboundmedicine.com/medline/citation/16393331/A_mutant_of_the_major_apple_allergen_Mal_d_1_demonstrating_hypo_allergenicity_in_the_target_organ_by_double_blind_placebo_controlled_food_challenge_ L2 - https://doi.org/10.1111/j.1365-2222.2005.02390.x DB - PRIME DP - Unbound Medicine ER -