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Turnip rape and oilseed rape are novel food allergens in children
Abstracts S167
J ALLERGY CLIN IMMUNOL VOLUME 115, NUMBER 2
E-CpG ODN: Immune Modulatory Therapy of Allergic Asthma
S. Jung1, M. Moon1, W. Park1, H. Lee2, D. Kim3; 1R&D Center of Pharmaceuticals, CJ Corp., Kyonggi-do, REPUBLIC OF KOREA, 2Chonbuk National University medical school, Department of Immunology, Chonju, REPUBLIC OF KOREA, 3Yonsei University, Seoul, REPUBLIC OF KOREA. Allergic asthma, unbalanced immune-mediated disease, is a highly prevalent and serious health problem for which no therapy currently offers the hope of a cure. CpG ODNs have been adapted to these allergic disease. However, artificial CpG ODNs may induce harmful and lethal shock effects because they have phosphorothioate(PS) modification to avoid the nuclease attacks and may enhance the induction of TNF-alpha and MIP-2. To develop novel therapeutic agent for allergic disease without severe side effects of PS-modificated artificial sequence, we have attempted to develop the specific ODN component derived from E.Coli(E-CpG ODN) having effective immunomodulatory function. Based on the understanding of CpG-ODNs that promote Th1 and regulatory-type immune responses, we examined the effects of CpG-ODN on an OVA-induced murine model of asthma. The E-CpG ODN derivatives inhibited eosinophil recruitment in OVA-induced airway, AHR and IgE production in association with reduction of Th2 cytokines such as IL-4 and IL-5 in BALF. Since Th2 response predominate in asthma and increase in Th1 response can prevent the differentiation of naïve Th0 response to Th2 response, we conclude that ECpG ODN can prevent the development of allergic airway disorder in the OVA-sensitized mouse model. These results suggest that E-CpG ODN may be a novel therapeutic tool for the treatment of allergic asthma. Funding: CJ Corp. Identification of 2S Albumin as an Allergen in Turnip Rape and Oilseed Rape T. Puumalainen1, A. Kotovuori2, S. Poikonen3, K. Vaali1, N. Kalkkinen2, T. Reunala3, K. Turjanmaa3, T. Palosuo1; 1National Public Health Institute, Helsinki, FINLAND, 2Institute of Biotechnology, University of Helsinki, Helsinki, FINLAND, 3Department of Dermatology, Tampere University Hospital, Tampere, FINLAND. RATIONALE: Food allergic children often react to seeds of turnip rape and oilseed rape in skin prick tests (SPT). Sensitization pathways are not known; children or their lactating mothers have not used these seeds in their diet. METHODS: Allergens from seeds of turnip rape and oilseed rape were purified using gel filtration and cation-exchange chromatography. The allergens were further characterized by mass spectrometric analyses and N-terminal sequencing. IgE binding of sera from 66 children with positive SPT to turnip rape and oilseed rape and 66 atopic controls with negative SPT were analyzed by IgE ELISA and immunoblotting. In vivo reactivity of the purified allergens was tested in 6 children with SPT. RESULTS: In IgE immunoblotting and IgE ELISA major reactivity was to a group of homologous, approximately 13 kDa proteins. These allergens were identified as 2S albumin, napins, according to N-terminal amino acid sequence and mass spectrometric analyses. In ELISA 66% of the patients gave a positive result. In SPT with purified napins a positive reaction was seen in all 6 children tested. CONCLUSIONS: This study shows that 2S albumins in turnip rape and oilseed rape are new food allergens. Studies are needed to clarify the ways of exposure and mechanisms of sensitization. Funding: National Public Health Institute
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Turnip Rape and Oilseed Rape Are Novel Food Allergens in Children S. Poikonen1, T. Puumalainen2, H. Kautiainen1, T. Palosuo2, T. Reunala1, K. Turjanmaa1; 1Department of Dermatology, Tampere University Hospi-
667
tal, Tampere, FINLAND, 2National Public Health Institute, Helsinki, FINLAND. RATIONALE: Young children with atopic eczema (AE) are frequently allergic to cow’s milk, egg and cereals, and sensitization to other foods is also possible. When 1887 children with AE were skin prick tested (SPT) to turnip rape (Brassica rapa) and oilseed rape (B. napus), 206 (10.9%) showed positive reactions. We now studied whether these children react also clinically. METHODS: Twenty-eight children (mean age 4.8 years) with positive SPT (≥5mm) to turnip rape or oilseed rape (seeds moistened in saline) were examined. Open challenge was started by applying crushed turnip rape seeds on the lips. If negative, increasing doses of turnip rape (from 10 to 900 mg) mixed in liquid food were given orally every 20 min. If negative, the child ate 1350 mg daily for six days. Twenty-five children with AE but negative SPT to turnip rape or oilseed rape served as controls in the labial challenge. Specific IgE was measured with immunoCAP (Pharmacia). RESULTS: Twenty-five (89%) children had a positive challenge reaction. Seventeen showed labial whealing and 4 facial urticaria or abdominal symptoms. In addition, 4 children showed delayed reactions such as flare-up of eczema or abdominal symptoms. All 25 control children were negative in the labial challenge. The median oilseed rape-specific IgE level was 16.3 kU/l in the 28 challenge positive children. CONCLUSIONS: Turnip rape and oilseed rape seem to be new important food allergens in young children with AE. A further study is needed to find out the origin of sensitization to these plant proteins. Funding: Tampere University Hospital Treatment of Egg Allergy in Children Through Oral Desensitization A. Buchanan1, S. M. Jones2,3, L. Christie2,3, K. M. Althage2,3, A. M. Sculrock2,3, R. M. Helm4, L. A. Pons1, S. Andrzejewski1, P. Steele1, A. W. Burks1; 1Pediatrics, Duke University Medical Center, Durham, NC, 2Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, 3Arkansas Children’s Hospital, Little Rock, AR, 4Microbiology, University of Arkansa for Medical Sciences, Little Rock, AR. RATIONALE: This study aims to determine if egg-allergic children can be orally desensitized to egg protein and if this desensitization will both protect them from reaction on accidental exposure to egg and help them outgrow their allergy faster. METHODS: Children diagnosed with egg allergy with serum CAP-FEIA to egg protein > 2 kU/L or positive egg challenge within six months and no history of anaphylactic reaction to egg are being enrolled into treatment and control groups. The control group follows an egg-elimination diet for the duration of the study. The treatment group undergoes an oral desensitization protocol to egg protein and then consumes a daily dose of egg protein at home. Blood draws occur at enrollment and follow-up to study effects of desensitization on the immune system. Two years after enrollment, both groups will undergo a double-blind-placebo-controlled food challenge to egg. RESULTS: To date, 12 subjects (mean enrollment age 4.8 years, range 14 months-13 years) and 5 controls have been enrolled. During the initial desensitization, 58% of subjects required antihistamine to treat symptoms. Most commonly affected organ systems are the GI tract or the upper respiratory tract. The subjects have been in the study for a mean of 9.8 months (range 1-19 months). CAP-FEIA to egg at baseline ranged from 0.36 - >100 Ku/L. 7 of 12 subjects have reached the final daily desensitization dose of 300mg. Only one subject required treatment for a reaction to his daily home dose. CONCLUSIONS: Oral desensitization to egg protein seems to be safe and well tolerated.
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J ALLERGY CLIN IMMUNOL VOLUME 115, NUMBER 2
E-CpG ODN: Immune Modulatory Therapy of Allergic Asthma
S. Jung1, M. Moon1, W. Park1, H. Lee2, D. Kim3; 1R&D Center of Pharmaceuticals, CJ Corp., Kyonggi-do, REPUBLIC OF KOREA, 2Chonbuk National University medical school, Department of Immunology, Chonju, REPUBLIC OF KOREA, 3Yonsei University, Seoul, REPUBLIC OF KOREA. Allergic asthma, unbalanced immune-mediated disease, is a highly prevalent and serious health problem for which no therapy currently offers the hope of a cure. CpG ODNs have been adapted to these allergic disease. However, artificial CpG ODNs may induce harmful and lethal shock effects because they have phosphorothioate(PS) modification to avoid the nuclease attacks and may enhance the induction of TNF-alpha and MIP-2. To develop novel therapeutic agent for allergic disease without severe side effects of PS-modificated artificial sequence, we have attempted to develop the specific ODN component derived from E.Coli(E-CpG ODN) having effective immunomodulatory function. Based on the understanding of CpG-ODNs that promote Th1 and regulatory-type immune responses, we examined the effects of CpG-ODN on an OVA-induced murine model of asthma. The E-CpG ODN derivatives inhibited eosinophil recruitment in OVA-induced airway, AHR and IgE production in association with reduction of Th2 cytokines such as IL-4 and IL-5 in BALF. Since Th2 response predominate in asthma and increase in Th1 response can prevent the differentiation of naïve Th0 response to Th2 response, we conclude that ECpG ODN can prevent the development of allergic airway disorder in the OVA-sensitized mouse model. These results suggest that E-CpG ODN may be a novel therapeutic tool for the treatment of allergic asthma. Funding: CJ Corp. Identification of 2S Albumin as an Allergen in Turnip Rape and Oilseed Rape T. Puumalainen1, A. Kotovuori2, S. Poikonen3, K. Vaali1, N. Kalkkinen2, T. Reunala3, K. Turjanmaa3, T. Palosuo1; 1National Public Health Institute, Helsinki, FINLAND, 2Institute of Biotechnology, University of Helsinki, Helsinki, FINLAND, 3Department of Dermatology, Tampere University Hospital, Tampere, FINLAND. RATIONALE: Food allergic children often react to seeds of turnip rape and oilseed rape in skin prick tests (SPT). Sensitization pathways are not known; children or their lactating mothers have not used these seeds in their diet. METHODS: Allergens from seeds of turnip rape and oilseed rape were purified using gel filtration and cation-exchange chromatography. The allergens were further characterized by mass spectrometric analyses and N-terminal sequencing. IgE binding of sera from 66 children with positive SPT to turnip rape and oilseed rape and 66 atopic controls with negative SPT were analyzed by IgE ELISA and immunoblotting. In vivo reactivity of the purified allergens was tested in 6 children with SPT. RESULTS: In IgE immunoblotting and IgE ELISA major reactivity was to a group of homologous, approximately 13 kDa proteins. These allergens were identified as 2S albumin, napins, according to N-terminal amino acid sequence and mass spectrometric analyses. In ELISA 66% of the patients gave a positive result. In SPT with purified napins a positive reaction was seen in all 6 children tested. CONCLUSIONS: This study shows that 2S albumins in turnip rape and oilseed rape are new food allergens. Studies are needed to clarify the ways of exposure and mechanisms of sensitization. Funding: National Public Health Institute
666
Turnip Rape and Oilseed Rape Are Novel Food Allergens in Children S. Poikonen1, T. Puumalainen2, H. Kautiainen1, T. Palosuo2, T. Reunala1, K. Turjanmaa1; 1Department of Dermatology, Tampere University Hospi-
667
tal, Tampere, FINLAND, 2National Public Health Institute, Helsinki, FINLAND. RATIONALE: Young children with atopic eczema (AE) are frequently allergic to cow’s milk, egg and cereals, and sensitization to other foods is also possible. When 1887 children with AE were skin prick tested (SPT) to turnip rape (Brassica rapa) and oilseed rape (B. napus), 206 (10.9%) showed positive reactions. We now studied whether these children react also clinically. METHODS: Twenty-eight children (mean age 4.8 years) with positive SPT (≥5mm) to turnip rape or oilseed rape (seeds moistened in saline) were examined. Open challenge was started by applying crushed turnip rape seeds on the lips. If negative, increasing doses of turnip rape (from 10 to 900 mg) mixed in liquid food were given orally every 20 min. If negative, the child ate 1350 mg daily for six days. Twenty-five children with AE but negative SPT to turnip rape or oilseed rape served as controls in the labial challenge. Specific IgE was measured with immunoCAP (Pharmacia). RESULTS: Twenty-five (89%) children had a positive challenge reaction. Seventeen showed labial whealing and 4 facial urticaria or abdominal symptoms. In addition, 4 children showed delayed reactions such as flare-up of eczema or abdominal symptoms. All 25 control children were negative in the labial challenge. The median oilseed rape-specific IgE level was 16.3 kU/l in the 28 challenge positive children. CONCLUSIONS: Turnip rape and oilseed rape seem to be new important food allergens in young children with AE. A further study is needed to find out the origin of sensitization to these plant proteins. Funding: Tampere University Hospital Treatment of Egg Allergy in Children Through Oral Desensitization A. Buchanan1, S. M. Jones2,3, L. Christie2,3, K. M. Althage2,3, A. M. Sculrock2,3, R. M. Helm4, L. A. Pons1, S. Andrzejewski1, P. Steele1, A. W. Burks1; 1Pediatrics, Duke University Medical Center, Durham, NC, 2Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, 3Arkansas Children’s Hospital, Little Rock, AR, 4Microbiology, University of Arkansa for Medical Sciences, Little Rock, AR. RATIONALE: This study aims to determine if egg-allergic children can be orally desensitized to egg protein and if this desensitization will both protect them from reaction on accidental exposure to egg and help them outgrow their allergy faster. METHODS: Children diagnosed with egg allergy with serum CAP-FEIA to egg protein > 2 kU/L or positive egg challenge within six months and no history of anaphylactic reaction to egg are being enrolled into treatment and control groups. The control group follows an egg-elimination diet for the duration of the study. The treatment group undergoes an oral desensitization protocol to egg protein and then consumes a daily dose of egg protein at home. Blood draws occur at enrollment and follow-up to study effects of desensitization on the immune system. Two years after enrollment, both groups will undergo a double-blind-placebo-controlled food challenge to egg. RESULTS: To date, 12 subjects (mean enrollment age 4.8 years, range 14 months-13 years) and 5 controls have been enrolled. During the initial desensitization, 58% of subjects required antihistamine to treat symptoms. Most commonly affected organ systems are the GI tract or the upper respiratory tract. The subjects have been in the study for a mean of 9.8 months (range 1-19 months). CAP-FEIA to egg at baseline ranged from 0.36 - >100 Ku/L. 7 of 12 subjects have reached the final daily desensitization dose of 300mg. Only one subject required treatment for a reaction to his daily home dose. CONCLUSIONS: Oral desensitization to egg protein seems to be safe and well tolerated.
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