- Email: [email protected]
Epicutaneous Immunotherapy (EPIT) for House Dust Mite (HDM) Allergy using VIASKIN® Technology: a Preclinical Study
Abstracts S177
J ALLERGY CLIN IMMUNOL VOLUME 123, NUMBER 2
Risks Associated with Foods Having Advisory Milk Labeling M. P. Crotty, S. L. Taylor; Food Allergy Research & Resource Program, University of Nebraska, Lincoln, NE. RATIONALE: Determine residual levels of milk in various packaged foods bearing advisory labeling (i.e. ‘‘may contain’’) and determine any potential risk for milk-allergic consumers. METHODS: Food products bearing advisory statements regarding milk were purchased in Lincoln, Nebraska, USA. A total of 100 products included 79 with allergy advisory labels, 15 with milk listed as a minor ingredient (last three ingredients on statement), 4 with milk fat listed as an ingredient and 2 with unique labeling. Products were categorized as baked goods/mixes, dark chocolate candy, other candy/confectionary, cereals, frozen desserts, instant meals, nutritional/granola bars, snack foods, and miscellaneous. Two different lot numbers of each product were obtained when possible (85 products) leading to a total of 185 samples. A representative sample from each package was homogenized and then analyzed for the presence of milk using a commercial enzyme - linked immunosorbent assay (Total Milk VeratoxÒ, Neogen) with a lower limit of quantification of 2.5 parts per million (ppm, mg/g). RESULTS: Milk was detected in at least one lot in 47% (47/100) of all products and in both lots in 24.7% (21/85) of cases. Of 147 samples with allergy advisory labels, 45 contained detectable milk (30.6%). Milk concentrations ranged from 3.4 to 4,800 ppm. Based on suggested serving sizes, estimated exposure doses ranged from 0.027 to 240 mg. Dark chocolate candy had the highest percentage with detectable milk in 77.3% (17/22) of samples. CONCLUSIONS: Many foods with advisory labeling contain detectable levels of milk. Milk-allergic consumers may be at risk if they consume these products.
677
Natural Course of Egg, Milk and Peanut Allergy Using a Novel Diagnostic Scheme: 1 Year Follow-Up in an Observational Study (CoFAR2) of Food Allergy S. H. Sicherer1, D. Stablein2, R. A. Wood3, A. W. Burks4, A. H. Liu5, S. M. Jones6, D. M. Fleischer5, D. Y. Leung5, R. Lindblad2, H. A. Sampson1 for the Consortium of Food Allergy Research1; 1Mt. Sinai School of Medicine, New York, NY, 2The EMMES Corporation, Rockville, MD, 3 Johns Hopkins University School of Medicine, New York, NY, 4Duke University Medical Center, Durham, NC, 5National Jewish Health, Denver, CO, 6University of Arkansas for Medical Sciences, Little Rock, AR. RATIONALE: We enrolled 3-15 month olds (n 5 512) with likely egg/ milk allergy without known current peanut allergy for an observational study of egg, milk and peanut allergy. Here we report 1 year follow-up using a novel diagnostic scheme. METHODS: A diagnostic scheme was developed and applied using foodspecific IgE levels, skin tests and clinical history/food challenge. Participants were diagnosed as ‘‘Allergic’’ (convincing histories/challenge/diagnostic tests), ‘‘Serologic diagnosis’’ (food never ingested but food-specific IgE exceeded diagnostic levels), ‘‘Potential allergy’’ (history/tests suggestive/not definitive of allergy), ‘‘Tolerant’’ and ‘‘non-IgE allergy’’. Transitions from categories ‘‘allergic/serologic’’ to ‘‘tolerant’’ were considered ‘‘resolved’’ and the reverse ‘‘developed’’ a food allergy. RESULTS: A total of 293 (median age at enrollment, 10 mo) subjects completed 1 year follow-up. Initial categories were: MILK- 48% allergic, 5% serologic diagnosis, 22% potential allergy and 25% tolerant; EGG29% allergic, 36% serologic, 23% potential, 13% tolerant; PEANUT0% allergic, 30% serologic, 38% potential, 33% tolerant. After one year, 17% resolved milk, 7% egg and 2% peanut. Rates of development of allergy were 3% for milk, 8% for egg and 3% for peanut. For those in the ‘‘potential’’ category at baseline, allergy was declared for 15% milk, 26% egg and 18% peanut, while tolerance was declared for 56% milk, 26% egg and 27% peanut. The one- year ‘‘allergic’’ rates were 42%, 31% and 4% for milk, egg and peanut, respectively. CONCLUSIONS: Applying a novel diagnostic scheme for 1 year, we observed few new allergies, but noted resolution/tolerance rates for milk that were twice those for egg.
678
Epicutaneous Immunotherapy (EPIT) for House Dust Mite (HDM) Allergy using VIASKINÒ Technology: a Preclinical Study L. Mondoulet1, P. Benhamou1, M. Ligouis1, S. Chariglione1, C. Dupont2; 1 DBV Technologies, PARIS, France, 2Hopital Saint Vincent de Paul, PARIS, France. RATIONALE: The efficacy of EPIT using VIASKINÒ technology was shown in pollen-, OVA- or peanut-sensitized mouse models (AAAAI 2008 and EAACI 2008). The aim of this study was to demonstrate the efficacy of EPIT on HDM-sensitized mice. METHODS: Four groups of BALB/c mice were studied, controls (C, n 5 10), sensitized-not treated (NT, n 5 9), sensitized and treated epicutaneously (EP, n 5 9), and sensitized-treated by subcutaneous route (SC, n 5 9). Sensitization was carried out by 2 subcutaneous injections (days 0 and 7) with HDM extracts, Dermatophagoides pteronyssinus (Der f) and farinae (Der p) and aluminium hydroxide adjuvant. Immunotherapy was performed once a week during 8 weeks by a 48 h application of both HDM extracts on the prepared skin in EP and subcutaneously in SC. Monitoring included specific IgE, IgG1 and IgG2a (ELISA), measurement of bronchial hyper-reactivity (pause enhancement (Penh), during plethysmography) and of bronchoalveolar lavage (BAL) cells. RESULTS: During immunotherapy, sIgG2a (Der.f/Der.p) increased in both treated groups, from 0.097/0.061 to 2.463/0.468 in EP and 0.099/ 0.075 to 2.009/0.726, in SC, p < 0.01. sIgE and sIgG1 did not vary. Penh during the challenge was lower in treated groups (158% of C values in EP and 141% in SC) than in NT (185%), p < 0.05. BAL eosinophils and lymphocytes significantly decreased in EP (6.9x104/1.0x105) and SC (3.3x104/4.1x104) as compared with NT (2.9x105/1.9 x105), p < 0.001. BAL neutrophils and macrophages did not vary. CONCLUSIONS: In HDM-sensitized mice, EPIT seems as efficient as SCIT.
679
Delayed Anaphylaxis and Urticaria Associated with Eating Mammalian Meat: Are IgE Antibodies to a Common Carbohydrate Capable of Mediating Systemic Reactions? S. P. Commins, S. M. Satinover, J. M. Roper, T. A. E. Platts-Mills; University of Virginia, Charlottesville, VA. RATIONALE: We have identified 20 patients with similar histories of anaphylaxis or urticaria 3-6 hours after the ingestion of beef, pork or lamb who have IgE ab to galactose-alpha-1,3-galactose (alpha-gal). Given the diagnostic challenges posed by delayed reactions, we performed in vivo (skin testing) and in vitro (basophil activation) studies to investigate these reactions. METHODS: Detailed histories were taken from adult patients presenting to the Allergy Clinic at the University of Virginia with recurrent anaphylaxis or urticaria. Skin prick tests (SPT), intradermal tests (ID) and basophil activation were performed. RESULTS: These patients had <4 mm reactions on SPT to mammalian meat using conventional extracts, whereas intradermal or fresh food SPT provided larger, more consistent wheal responses. Interestingly, inhibition-radioimmunoassays using alpha-gal showed increased levels of alpha-gal in fresh extracts of beef, pork and lamb used for SPT compared to commercial reagents. Patients did not report symptoms after eating fish, turkey or chicken and had negative SPT to these foods. Inhibition-radioimmunoassays of extracts (commercial and fresh) of fish, turkey or chicken were negative for alpha-gal. Moreover, blood from patients with IgE ab to alpha-gal had increased expression of CD203c on the surface of basophils in response to alpha-gal and beef thyroglobulin compared to that of controls. CONCLUSIONS: In vivo testing of patients with IgE ab to alpha-gal indicated that SPT using fresh extracts of mammalian meat was superior to commercial reagents and is likely explained by the increased presence of alpha-gal, while in vitro studies showed that IgE ab to this carbohydrate can produce basophil activation.
MONDAY
676
J ALLERGY CLIN IMMUNOL VOLUME 123, NUMBER 2
Risks Associated with Foods Having Advisory Milk Labeling M. P. Crotty, S. L. Taylor; Food Allergy Research & Resource Program, University of Nebraska, Lincoln, NE. RATIONALE: Determine residual levels of milk in various packaged foods bearing advisory labeling (i.e. ‘‘may contain’’) and determine any potential risk for milk-allergic consumers. METHODS: Food products bearing advisory statements regarding milk were purchased in Lincoln, Nebraska, USA. A total of 100 products included 79 with allergy advisory labels, 15 with milk listed as a minor ingredient (last three ingredients on statement), 4 with milk fat listed as an ingredient and 2 with unique labeling. Products were categorized as baked goods/mixes, dark chocolate candy, other candy/confectionary, cereals, frozen desserts, instant meals, nutritional/granola bars, snack foods, and miscellaneous. Two different lot numbers of each product were obtained when possible (85 products) leading to a total of 185 samples. A representative sample from each package was homogenized and then analyzed for the presence of milk using a commercial enzyme - linked immunosorbent assay (Total Milk VeratoxÒ, Neogen) with a lower limit of quantification of 2.5 parts per million (ppm, mg/g). RESULTS: Milk was detected in at least one lot in 47% (47/100) of all products and in both lots in 24.7% (21/85) of cases. Of 147 samples with allergy advisory labels, 45 contained detectable milk (30.6%). Milk concentrations ranged from 3.4 to 4,800 ppm. Based on suggested serving sizes, estimated exposure doses ranged from 0.027 to 240 mg. Dark chocolate candy had the highest percentage with detectable milk in 77.3% (17/22) of samples. CONCLUSIONS: Many foods with advisory labeling contain detectable levels of milk. Milk-allergic consumers may be at risk if they consume these products.
677
Natural Course of Egg, Milk and Peanut Allergy Using a Novel Diagnostic Scheme: 1 Year Follow-Up in an Observational Study (CoFAR2) of Food Allergy S. H. Sicherer1, D. Stablein2, R. A. Wood3, A. W. Burks4, A. H. Liu5, S. M. Jones6, D. M. Fleischer5, D. Y. Leung5, R. Lindblad2, H. A. Sampson1 for the Consortium of Food Allergy Research1; 1Mt. Sinai School of Medicine, New York, NY, 2The EMMES Corporation, Rockville, MD, 3 Johns Hopkins University School of Medicine, New York, NY, 4Duke University Medical Center, Durham, NC, 5National Jewish Health, Denver, CO, 6University of Arkansas for Medical Sciences, Little Rock, AR. RATIONALE: We enrolled 3-15 month olds (n 5 512) with likely egg/ milk allergy without known current peanut allergy for an observational study of egg, milk and peanut allergy. Here we report 1 year follow-up using a novel diagnostic scheme. METHODS: A diagnostic scheme was developed and applied using foodspecific IgE levels, skin tests and clinical history/food challenge. Participants were diagnosed as ‘‘Allergic’’ (convincing histories/challenge/diagnostic tests), ‘‘Serologic diagnosis’’ (food never ingested but food-specific IgE exceeded diagnostic levels), ‘‘Potential allergy’’ (history/tests suggestive/not definitive of allergy), ‘‘Tolerant’’ and ‘‘non-IgE allergy’’. Transitions from categories ‘‘allergic/serologic’’ to ‘‘tolerant’’ were considered ‘‘resolved’’ and the reverse ‘‘developed’’ a food allergy. RESULTS: A total of 293 (median age at enrollment, 10 mo) subjects completed 1 year follow-up. Initial categories were: MILK- 48% allergic, 5% serologic diagnosis, 22% potential allergy and 25% tolerant; EGG29% allergic, 36% serologic, 23% potential, 13% tolerant; PEANUT0% allergic, 30% serologic, 38% potential, 33% tolerant. After one year, 17% resolved milk, 7% egg and 2% peanut. Rates of development of allergy were 3% for milk, 8% for egg and 3% for peanut. For those in the ‘‘potential’’ category at baseline, allergy was declared for 15% milk, 26% egg and 18% peanut, while tolerance was declared for 56% milk, 26% egg and 27% peanut. The one- year ‘‘allergic’’ rates were 42%, 31% and 4% for milk, egg and peanut, respectively. CONCLUSIONS: Applying a novel diagnostic scheme for 1 year, we observed few new allergies, but noted resolution/tolerance rates for milk that were twice those for egg.
678
Epicutaneous Immunotherapy (EPIT) for House Dust Mite (HDM) Allergy using VIASKINÒ Technology: a Preclinical Study L. Mondoulet1, P. Benhamou1, M. Ligouis1, S. Chariglione1, C. Dupont2; 1 DBV Technologies, PARIS, France, 2Hopital Saint Vincent de Paul, PARIS, France. RATIONALE: The efficacy of EPIT using VIASKINÒ technology was shown in pollen-, OVA- or peanut-sensitized mouse models (AAAAI 2008 and EAACI 2008). The aim of this study was to demonstrate the efficacy of EPIT on HDM-sensitized mice. METHODS: Four groups of BALB/c mice were studied, controls (C, n 5 10), sensitized-not treated (NT, n 5 9), sensitized and treated epicutaneously (EP, n 5 9), and sensitized-treated by subcutaneous route (SC, n 5 9). Sensitization was carried out by 2 subcutaneous injections (days 0 and 7) with HDM extracts, Dermatophagoides pteronyssinus (Der f) and farinae (Der p) and aluminium hydroxide adjuvant. Immunotherapy was performed once a week during 8 weeks by a 48 h application of both HDM extracts on the prepared skin in EP and subcutaneously in SC. Monitoring included specific IgE, IgG1 and IgG2a (ELISA), measurement of bronchial hyper-reactivity (pause enhancement (Penh), during plethysmography) and of bronchoalveolar lavage (BAL) cells. RESULTS: During immunotherapy, sIgG2a (Der.f/Der.p) increased in both treated groups, from 0.097/0.061 to 2.463/0.468 in EP and 0.099/ 0.075 to 2.009/0.726, in SC, p < 0.01. sIgE and sIgG1 did not vary. Penh during the challenge was lower in treated groups (158% of C values in EP and 141% in SC) than in NT (185%), p < 0.05. BAL eosinophils and lymphocytes significantly decreased in EP (6.9x104/1.0x105) and SC (3.3x104/4.1x104) as compared with NT (2.9x105/1.9 x105), p < 0.001. BAL neutrophils and macrophages did not vary. CONCLUSIONS: In HDM-sensitized mice, EPIT seems as efficient as SCIT.
679
Delayed Anaphylaxis and Urticaria Associated with Eating Mammalian Meat: Are IgE Antibodies to a Common Carbohydrate Capable of Mediating Systemic Reactions? S. P. Commins, S. M. Satinover, J. M. Roper, T. A. E. Platts-Mills; University of Virginia, Charlottesville, VA. RATIONALE: We have identified 20 patients with similar histories of anaphylaxis or urticaria 3-6 hours after the ingestion of beef, pork or lamb who have IgE ab to galactose-alpha-1,3-galactose (alpha-gal). Given the diagnostic challenges posed by delayed reactions, we performed in vivo (skin testing) and in vitro (basophil activation) studies to investigate these reactions. METHODS: Detailed histories were taken from adult patients presenting to the Allergy Clinic at the University of Virginia with recurrent anaphylaxis or urticaria. Skin prick tests (SPT), intradermal tests (ID) and basophil activation were performed. RESULTS: These patients had <4 mm reactions on SPT to mammalian meat using conventional extracts, whereas intradermal or fresh food SPT provided larger, more consistent wheal responses. Interestingly, inhibition-radioimmunoassays using alpha-gal showed increased levels of alpha-gal in fresh extracts of beef, pork and lamb used for SPT compared to commercial reagents. Patients did not report symptoms after eating fish, turkey or chicken and had negative SPT to these foods. Inhibition-radioimmunoassays of extracts (commercial and fresh) of fish, turkey or chicken were negative for alpha-gal. Moreover, blood from patients with IgE ab to alpha-gal had increased expression of CD203c on the surface of basophils in response to alpha-gal and beef thyroglobulin compared to that of controls. CONCLUSIONS: In vivo testing of patients with IgE ab to alpha-gal indicated that SPT using fresh extracts of mammalian meat was superior to commercial reagents and is likely explained by the increased presence of alpha-gal, while in vitro studies showed that IgE ab to this carbohydrate can produce basophil activation.
MONDAY
676