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Oral Peanut Immunotherapy for Children with Peanut Allergy
S136 Abstracts
J ALLERGY CLIN IMMUNOL FEBRUARY 2008
SUNDAY
526
528
527
529
Plasmacytoid Dendritic Cells from Asthma Patients Secrete Less Interferon-a Upon Exposure to Respiratory Viruses M. A. Gill, G. Bajwa, N. Jiang, J. Teeple, I. Dougherty, R. Gruchalla; UT Southwestern Medical Center at Dallas, Dallas, TX. RATIONALE: The purpose of this study was to determine the capacity of plasmacytoid dendritic cells (pDCs) from asthmatic individuals to secrete interferon-alpha (IFN-a) in response to viral exposure. METHODS: Blood pDCs from 5 patients with allergic asthma and 4 healthy control subjects were purified using antibody-coated magnetic microbeads (Miltenyi Biotec) and cultured for 36 hours with either no virus, respiratory syncytial virus (RSV), or influenza A. IFN-a concentrations in the pDC culture supernatants were subsequently determined by ELISA. Additionally, the expression of FceRI on blood pDCs was determined by staining with fluorochrome-labeled monoclonal antibodies and subsequent flow cytometry analysis. RESULTS: The mean concentration of IFN-a secreted by purified pDCs exposed to RSV was 264 6 72 pg/ml in asthmatic patients and 1837 6 574 pg/ml in controls (p 5 0.02). After exposure to influenza A, the mean concentration of IFN-a secreted by purified pDCs was 3060 6 1780 pg/ml in asthmatic patients versus 4210 6 1540 pg/ml in the controls (p 5 0.14). A negative correlation between the pDC FceRI expression and RSVinduced IFN-a secretion was observed in the asthmatic patients only (correlation coefficient 5 -0.89; p 5 0.1). CONCLUSIONS: Blood pDCs purified from patients with allergic asthma secrete significantly less IFN-a in response to RSV exposure than pDCs purifed from healthy controls. A similar reduction in IFN-a secretion was also observed after influenza A exposure, although it was not significant. These data suggest that allergic asthma affects the capacity of pDCs to secrete IFN-a in response to single-stranded RNA viruses. Funding: NIH Mean Wheal Size from Peanut Prick Skin Test and IgE Levels in Peanut Allergic Patients Receiving Oral Peanut Immunotherapy M. A. Adair1, S. S. Laubach1, P. Steele1, J. Kamilaris1, L. Pons1, M. Kulis1, A. M. Scurlock2, S. M. Jones2, A. W. Burks1; 1Duke University, Durham, NC, 2Arkansas Children’s Hospital, Little Rock, AR. RATIONALE: Oral immunotherapy (OIT) for peanut allergy is in clinical pilot studies. The relationship between prick skin test results and serum specific peanut IgE levels could be important clinical markers for tolerance. METHODS: Peanut-allergic children aged 1 to 16 years underwent a standard OIT protocol, with two cohorts achieving a maintenance dose of either 300 mg or up to 1800 mg peanut protein daily. An open food challenge (OFC) was used to determine tolerance. Peanut-specific serum IgE and titrated skin prick testing (SPT) were performed at 0, 6, 12, 18, and 24 months. The wheal diameter was defined as the mean of the longest and its perpendicular diameter. RESULTS: Twenty-two patients have received peanut OIT for at least 12 months. The wheal diameter from peanut SPT significantly decreased in size (p < 0.0001) over this time period. Moreover, the 1:20 concentration, which is typically used in the clinical setting, resulted in significantly larger changes in wheal diameter sooner after the start of OIT than the lower concentration SPT (p < 0.0001). In the first cohort followed for 2 years, 86% exhibited a positive 1:20 SPT (5 mm) at baseline whereas by 24 months only 43% still had positive SPT. After accounting for patient, cohort, and time, there was no significant correlation found between wheal size and IgE levels. CONCLUSIONS: In children receiving peanut OIT, the average peanut SPT significantly decreased. There was no significant correlation found between wheal size and IgE levels. Correlation with clinical tolerance will be determined after completion of food challenges. Funding: Duke University Allergy Immunology Department
Rush Specific Oral Tolerance Induction in Peanut Allergic Patients with High Risk of Anaphylactic Reactions K. Blumchen, U. Staden, H. Ulbricht, N. Blanckenstein, K. Dobberstein, U. Wahn, B. Niggemann, K. Beyer; Pediatric Pneumology and Immunology, Charite, Berlin, GERMANY. RATIONALE: Up to now the only treatment option for peanut allergic children is strict avoidance. Specific oral tolerance induction (SOTI) using a rush protocol would be a new therapeutic approach for these patients. METHODS: Six peanut sensitized patients, age 3 to 10 years (median 5.7 years) were recruited. Peanut-specific IgE ranged from 85 kU/l to >100 kU/l (median >100 kU/l). All patients were asthmatic and had a high risk for peanut-induced anaphylactic reactions. Peanut allergy was confirmed by double-blind placebo controlled peanut challenge (DBPCFC). After challenge, on an inpatient basis children received 3-4 increasing doses of peanut per day for six days starting at 1/100 of their positive challenge dose. RESULTS: On DBPCFC patients reacted at a median cumulative dose of 0.47 g peanut (0.47-1.96 g). During Rush-SOTI children showed allergic reactions at a lower cumulative dose of 0.26 g peanut (range: 0.096-0.48 g). Allergic symptoms were frequent during Rush-SOTI. Patients developed hives (4/6), vomiting (3/6), diarrhoea (1/6) and/or coughing (3/6). After six days patients were discharged with a dose ranged from 0.024-0.16 g (median 0.16 g peanut) for daily consumption. Further increases in dose are planed on an outpatient basis. CONCLUSIONS: Peanut allergic patients at high risk for anaphylactic reactions experienced frequent side effects during Rush-SOTI. A protective dose of peanut allergen could not be reached during this short time period. Additional increases in dose appear to be necessary over an extended period. Whether modified protocols would be beneficial in regard to the frequency of side effects needs to be shown. Funding: Food Allergy and Anaphylaxis Network (FAAN)
Oral Peanut Immunotherapy for Children with Peanut Allergy S. D. Nash1, P. H. Steele1, J. S. Kamilaris1, L. Pons1, M. D. Kulis1, L. A. Lee1, A. M. Scurlock2, K. P. Palmer2, T. T. Perry2, S. M. Jones2, A. W. Burks1; 1Duke University Medical Center, Durham, NC, 2University of Arkansas for Medical Sciences, Little Rock, AR. RATIONALE: The goal of our study was to determine if peanut oral immunotherapy (OIT) can desensitize peanut allergic children to peanut protein. METHODS: The study included children with a clinical history of peanut allergy and peanut specific IgE 15 kU/L. The study was divided into 3 phases; a modified rush initial day of multiple doses (0.1 mg to 50 mg peanut doses), a build up phase of daily doses, increasing the dose every 2 weeks, and a daily maintenance phase for 4 months (dose of 300 mg peanut protein) followed by an open food challenge (OFC) using peanut flour (7.8 gms). Peanut specific IgE, IgG, and IgG4 were measured at specific intervals. RESULTS: Thirteen children completed the study and have undergone OFC. All subjects tolerated the full OFC (7.8 gms peanut flour) Eight subjects had no symptoms. Five subjects experienced mild symptoms with four being treated with diphenhydramine. During the modified rush phase most subjects had mild allergic symptoms but two subjects experienced significant, systemic allergic symptoms. The initial mean peanut specific IgE was 184 kU/L (range 11 to 401). Peanut specific IgE levels increased significantly at 3 months (p 5 .016) and six months (p 5 .039) and then declined. Peanut specific IgG was increased significantly from baseline at 3 months (p 5 .016) and at 8 months (p 5 .033). Peanut specific IgG4 was increased significantly at 3 months (p 5 .016) and 6 months (p 5 .004) but not at open challenge. CONCLUSION: Peanut OIT is effective for decreasing the risk of a significant allergic reaction after accidental peanut ingestion. Immunologic changes correlate with other forms of allergen-specific immunotherapy. Funding: Duke University Medical Center
J ALLERGY CLIN IMMUNOL FEBRUARY 2008
SUNDAY
526
528
527
529
Plasmacytoid Dendritic Cells from Asthma Patients Secrete Less Interferon-a Upon Exposure to Respiratory Viruses M. A. Gill, G. Bajwa, N. Jiang, J. Teeple, I. Dougherty, R. Gruchalla; UT Southwestern Medical Center at Dallas, Dallas, TX. RATIONALE: The purpose of this study was to determine the capacity of plasmacytoid dendritic cells (pDCs) from asthmatic individuals to secrete interferon-alpha (IFN-a) in response to viral exposure. METHODS: Blood pDCs from 5 patients with allergic asthma and 4 healthy control subjects were purified using antibody-coated magnetic microbeads (Miltenyi Biotec) and cultured for 36 hours with either no virus, respiratory syncytial virus (RSV), or influenza A. IFN-a concentrations in the pDC culture supernatants were subsequently determined by ELISA. Additionally, the expression of FceRI on blood pDCs was determined by staining with fluorochrome-labeled monoclonal antibodies and subsequent flow cytometry analysis. RESULTS: The mean concentration of IFN-a secreted by purified pDCs exposed to RSV was 264 6 72 pg/ml in asthmatic patients and 1837 6 574 pg/ml in controls (p 5 0.02). After exposure to influenza A, the mean concentration of IFN-a secreted by purified pDCs was 3060 6 1780 pg/ml in asthmatic patients versus 4210 6 1540 pg/ml in the controls (p 5 0.14). A negative correlation between the pDC FceRI expression and RSVinduced IFN-a secretion was observed in the asthmatic patients only (correlation coefficient 5 -0.89; p 5 0.1). CONCLUSIONS: Blood pDCs purified from patients with allergic asthma secrete significantly less IFN-a in response to RSV exposure than pDCs purifed from healthy controls. A similar reduction in IFN-a secretion was also observed after influenza A exposure, although it was not significant. These data suggest that allergic asthma affects the capacity of pDCs to secrete IFN-a in response to single-stranded RNA viruses. Funding: NIH Mean Wheal Size from Peanut Prick Skin Test and IgE Levels in Peanut Allergic Patients Receiving Oral Peanut Immunotherapy M. A. Adair1, S. S. Laubach1, P. Steele1, J. Kamilaris1, L. Pons1, M. Kulis1, A. M. Scurlock2, S. M. Jones2, A. W. Burks1; 1Duke University, Durham, NC, 2Arkansas Children’s Hospital, Little Rock, AR. RATIONALE: Oral immunotherapy (OIT) for peanut allergy is in clinical pilot studies. The relationship between prick skin test results and serum specific peanut IgE levels could be important clinical markers for tolerance. METHODS: Peanut-allergic children aged 1 to 16 years underwent a standard OIT protocol, with two cohorts achieving a maintenance dose of either 300 mg or up to 1800 mg peanut protein daily. An open food challenge (OFC) was used to determine tolerance. Peanut-specific serum IgE and titrated skin prick testing (SPT) were performed at 0, 6, 12, 18, and 24 months. The wheal diameter was defined as the mean of the longest and its perpendicular diameter. RESULTS: Twenty-two patients have received peanut OIT for at least 12 months. The wheal diameter from peanut SPT significantly decreased in size (p < 0.0001) over this time period. Moreover, the 1:20 concentration, which is typically used in the clinical setting, resulted in significantly larger changes in wheal diameter sooner after the start of OIT than the lower concentration SPT (p < 0.0001). In the first cohort followed for 2 years, 86% exhibited a positive 1:20 SPT (5 mm) at baseline whereas by 24 months only 43% still had positive SPT. After accounting for patient, cohort, and time, there was no significant correlation found between wheal size and IgE levels. CONCLUSIONS: In children receiving peanut OIT, the average peanut SPT significantly decreased. There was no significant correlation found between wheal size and IgE levels. Correlation with clinical tolerance will be determined after completion of food challenges. Funding: Duke University Allergy Immunology Department
Rush Specific Oral Tolerance Induction in Peanut Allergic Patients with High Risk of Anaphylactic Reactions K. Blumchen, U. Staden, H. Ulbricht, N. Blanckenstein, K. Dobberstein, U. Wahn, B. Niggemann, K. Beyer; Pediatric Pneumology and Immunology, Charite, Berlin, GERMANY. RATIONALE: Up to now the only treatment option for peanut allergic children is strict avoidance. Specific oral tolerance induction (SOTI) using a rush protocol would be a new therapeutic approach for these patients. METHODS: Six peanut sensitized patients, age 3 to 10 years (median 5.7 years) were recruited. Peanut-specific IgE ranged from 85 kU/l to >100 kU/l (median >100 kU/l). All patients were asthmatic and had a high risk for peanut-induced anaphylactic reactions. Peanut allergy was confirmed by double-blind placebo controlled peanut challenge (DBPCFC). After challenge, on an inpatient basis children received 3-4 increasing doses of peanut per day for six days starting at 1/100 of their positive challenge dose. RESULTS: On DBPCFC patients reacted at a median cumulative dose of 0.47 g peanut (0.47-1.96 g). During Rush-SOTI children showed allergic reactions at a lower cumulative dose of 0.26 g peanut (range: 0.096-0.48 g). Allergic symptoms were frequent during Rush-SOTI. Patients developed hives (4/6), vomiting (3/6), diarrhoea (1/6) and/or coughing (3/6). After six days patients were discharged with a dose ranged from 0.024-0.16 g (median 0.16 g peanut) for daily consumption. Further increases in dose are planed on an outpatient basis. CONCLUSIONS: Peanut allergic patients at high risk for anaphylactic reactions experienced frequent side effects during Rush-SOTI. A protective dose of peanut allergen could not be reached during this short time period. Additional increases in dose appear to be necessary over an extended period. Whether modified protocols would be beneficial in regard to the frequency of side effects needs to be shown. Funding: Food Allergy and Anaphylaxis Network (FAAN)
Oral Peanut Immunotherapy for Children with Peanut Allergy S. D. Nash1, P. H. Steele1, J. S. Kamilaris1, L. Pons1, M. D. Kulis1, L. A. Lee1, A. M. Scurlock2, K. P. Palmer2, T. T. Perry2, S. M. Jones2, A. W. Burks1; 1Duke University Medical Center, Durham, NC, 2University of Arkansas for Medical Sciences, Little Rock, AR. RATIONALE: The goal of our study was to determine if peanut oral immunotherapy (OIT) can desensitize peanut allergic children to peanut protein. METHODS: The study included children with a clinical history of peanut allergy and peanut specific IgE 15 kU/L. The study was divided into 3 phases; a modified rush initial day of multiple doses (0.1 mg to 50 mg peanut doses), a build up phase of daily doses, increasing the dose every 2 weeks, and a daily maintenance phase for 4 months (dose of 300 mg peanut protein) followed by an open food challenge (OFC) using peanut flour (7.8 gms). Peanut specific IgE, IgG, and IgG4 were measured at specific intervals. RESULTS: Thirteen children completed the study and have undergone OFC. All subjects tolerated the full OFC (7.8 gms peanut flour) Eight subjects had no symptoms. Five subjects experienced mild symptoms with four being treated with diphenhydramine. During the modified rush phase most subjects had mild allergic symptoms but two subjects experienced significant, systemic allergic symptoms. The initial mean peanut specific IgE was 184 kU/L (range 11 to 401). Peanut specific IgE levels increased significantly at 3 months (p 5 .016) and six months (p 5 .039) and then declined. Peanut specific IgG was increased significantly from baseline at 3 months (p 5 .016) and at 8 months (p 5 .033). Peanut specific IgG4 was increased significantly at 3 months (p 5 .016) and 6 months (p 5 .004) but not at open challenge. CONCLUSION: Peanut OIT is effective for decreasing the risk of a significant allergic reaction after accidental peanut ingestion. Immunologic changes correlate with other forms of allergen-specific immunotherapy. Funding: Duke University Medical Center