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Adiponectin Influences the Effects of Acrolein On T Cells of Atopic Individuals in Vitro
AB194 Abstracts
692
Adiponectin Influences the Effects of Acrolein On T Cells of Atopic Individuals in Vitro Christina E. Ciaccio, MD, Brianna Stecklein, Lanny Rosenwasser, MD, FAAAAI; Children’s Mercy Hospital, Kansas City, MO. RATIONALE: Acrolein is an alpha-beta unsaturated aldehyde found in high levels in environmental tobacco smoke and has previously been shown to be immunologically active. Considerable variability exists, however, in individual’s response to tobacco smoke exposure. Adiponectin is an adipose related cytokine which has been found to have a variety of anti-inflammatory effects. Levels of this cytokine decrease with increased adiposity. We therefore aimed to determine the effect of adiponectin on peripheral blood mononuclear cells (PBMC) that have been exposed to acrolein. METHODS: PBMC were isolated from heparinized blood drawn from atopic individuals. Cells were stimulated with anti-CD3/anti-CD28 coated beads and cultured in the presence of acrolein with and without adiponectin. Cells were stained and fixed on day 7. Viability, proliferation and cell surface marker expression were monitored by flow cytometry. RESULTS: Acrolein proportionally inhibits proliferation of CD3+ cells starting at a concentration of 10mM and increasing until near complete suppression is achieved at 20mM (93% inhibition, p<0.05). When cells were pretreated with adiponectin, however, this inhibition was completely suppressed (7% inhibition, p<0.017). CONCLUSIONS: Adiponectin attenuates the effects of the tobacco smoke component, acrolein on CD3+ T cells in vitro. This observation provides evidence that body composition may contribute to the immunologic response to tobacco smoke and provides a possible mechanism for the varying affects of tobacco smoke on exposed individuals.
693
MONDAY
Inter-Individual Variations of the Specific Immune Response to Peanut Allergic Components: Prospect for Specific Therapy Eric Wambre, PhD1, Eddie A. James1, David Robinson2, William W. Kwok, PhD1,3; 1Benaroya Research Institute at Virginia Mason, Seattle, WA, 2Virginia Mason Medical Center, 3Department of Medicine, University of Washington. RATIONALE: Peanuts proteins comprised of at least 10 allergic components. The contribution to specific immune responses by each component in each individual is not known. Details characterisation of immune response to allergic components of peanut is required to develop suitable immunotherapeutic strategies. METHODS: Pools of 20-mer peptides spanning the entire sequence of Ara h 1, 2, 3, 6, 8 and 9 protein were used to determine T cell reactivity. CD154-based assay was used in an ex vivo approach to assess at a single cell level the peanut allergen-specific CD4+ T cell responses in peanut allergic individuals. Analysis of the frequency, surface marker phenotype and cytokine profile of these cells was performed to study the mechanism involved in peanut allergic inflammation. A correlation between specific immune response to each peanut allergic component and contribution to clinical symptoms was also evaluated. RESULTS: We observed in our study population inter-individual variations in immunogenicity and type of specific CD4+ T cell immune response to peanut allergic components. Differential ability of the allergic individual to respond to peanut allergic allergens appears to be influenced by HLA class II allele polymorphisms. CONCLUSIONS: Ability to identify immunogenicity and type of response elicited by each peanut allergic component appears to be critical to future success in vaccine development against peanut allergy. Understanding the type of cellular response and the role of genetic restriction may allow to target immune response to critical peanut allergen and to uncover the optimal type of cellular immune response necessary for protection.
J ALLERGY CLIN IMMUNOL FEBRUARY 2013
694
Serum Periostin Levels Correlate with Bronchial Hyperresponsiveness to Mannitol and Methacholine in Children with Asthma Heysung Baek, MD, PhD1, Jae-Won Oh, MD, PhD, FAAAAI2, Ha-Baik Lee, MD, PhD2, Kenji Izuhara, MD, PhD3; 1Hallym University College of Medicine, Seoul, Korea, 2Hanyang University College of Medicine, Seoul, Korea, 3Saga Medical School, Saga, Japan. RATIONALE: Recently it has been found that periostin, a matricellular protein, is a highly inducible product of IL-4 or IL-13 in lung fibroblasts and is involved in fibrosis of bronchial asthma. Effects of serum periostin on bronchial hyperresponsiveness (BHR) have not yet been demonstrated in the human airway. The aim of this study was to address the relationship between serum periostin and BHR in children with asthma. METHODS: Eighty-three children between the ages of 6 and 15 years were included and comprised the asthmatic group (n 5 54) and healthy control group (n 5 29). We measured fractional exhaled nitric oxide (FENO) and serum periostin levels. We performed mannitol and methacholine provocation challenges. The response to methacholine was expressed as a provocative concentration causing a 20% decrease in FEV1 (PC20). The response to mannitol was expressed as a provocative dose causing a 15% fall in FEV1 (PD15) and the response–dose ratio (RDR). RESULTS: Children with asthma had a significantly higher mean (6 SD) level of periostin than controls (78.59 6 17.43 vs. 70.68 6 14.08 ng/mL; P 5 0.034). The serum periostin levels were significantly correlated with FENO (r 5 0.318, P 5 0.023). Serum periostin levels significantly correlate with methacholine PC20 (r 5 -0.325, P 5 0.047) and mannitol PD15 (r 5 -0.391, P 5 0.027) and RDR mannitol (r 5 0.351, P 5 0.023). CONCLUSIONS: Serum periostin levels were increased in asthmatic children and were related to BHR to methacholine and mannitol.
695
Meta Analysis of Asthma Exacerbation Rates in Pediatric Studies During Asthma Managed Using Fractional Exhaled Nitric Oxide Versus Standard Clinical Parameters Alone Joseph D. Spahn, MD1, Jonathan Malka, MD2, Todd A. Mahr, MD, FAAAAI3, Paul M. Dorinsky, MD4; 1National Jewish Health, Denver, CO, 2Pediatric Associates, Aventura, FL, 3Gundersen Lutheran Medical Center, La Crosse, WI, 4Aerocrine, Inc., Morrisville, NC. RATIONALE: A Cochrane Meta-analysis of fractional exhaled nitric oxide (FeNO) versus standard clinical management was published in 2009 (Petsky et al). The primary endpoint was the number of subjects with asthma exacerbations. However, the rate of asthma exacerbations is considered to be the most appropriate endpoint for assessing exacerbations as it takes into account subjects who have multiple exacerbations. Since the original Cochrane Meta-analysis included this information for only 1 of 3 pediatric asthma management studies, the data was reanalyzed to include all 3 pediatric studies from the Cochrane data set. METHODS: Meta-analysis of asthma exacerbation rates in pediatric studies evaluating asthma managed using FeNO versus standard clinical parameters alone. All three available pediatric studies from the original Cochrane data set were included. The methodology for the analysis of exacerbation rates was the same as for the original Cochrane analyses. RESULTS: Across the 3 studies, there were a total of 393 pediatric subjects in the FeNO management group and 389 subjects in the control management group. Asthma exacerbation rates ranged from 0.18-0.66 and 0.25-0.84 across the FeNO and control management groups, respectively. A meta-analysis of exacerbation rates indicates that the exacerbation rate was significantly reduced in favor of the FeNO-based asthma management in children (mean treatment difference 5 -0.11; 95% CI [-0.21, -0.02]). CONCLUSIONS: The data from this meta-analysis in pediatric subjects with asthma indicates that FeNO guided asthma management is a more effective strategy for managing pediatric asthma than the use of clinical parameters alone.
692
Adiponectin Influences the Effects of Acrolein On T Cells of Atopic Individuals in Vitro Christina E. Ciaccio, MD, Brianna Stecklein, Lanny Rosenwasser, MD, FAAAAI; Children’s Mercy Hospital, Kansas City, MO. RATIONALE: Acrolein is an alpha-beta unsaturated aldehyde found in high levels in environmental tobacco smoke and has previously been shown to be immunologically active. Considerable variability exists, however, in individual’s response to tobacco smoke exposure. Adiponectin is an adipose related cytokine which has been found to have a variety of anti-inflammatory effects. Levels of this cytokine decrease with increased adiposity. We therefore aimed to determine the effect of adiponectin on peripheral blood mononuclear cells (PBMC) that have been exposed to acrolein. METHODS: PBMC were isolated from heparinized blood drawn from atopic individuals. Cells were stimulated with anti-CD3/anti-CD28 coated beads and cultured in the presence of acrolein with and without adiponectin. Cells were stained and fixed on day 7. Viability, proliferation and cell surface marker expression were monitored by flow cytometry. RESULTS: Acrolein proportionally inhibits proliferation of CD3+ cells starting at a concentration of 10mM and increasing until near complete suppression is achieved at 20mM (93% inhibition, p<0.05). When cells were pretreated with adiponectin, however, this inhibition was completely suppressed (7% inhibition, p<0.017). CONCLUSIONS: Adiponectin attenuates the effects of the tobacco smoke component, acrolein on CD3+ T cells in vitro. This observation provides evidence that body composition may contribute to the immunologic response to tobacco smoke and provides a possible mechanism for the varying affects of tobacco smoke on exposed individuals.
693
MONDAY
Inter-Individual Variations of the Specific Immune Response to Peanut Allergic Components: Prospect for Specific Therapy Eric Wambre, PhD1, Eddie A. James1, David Robinson2, William W. Kwok, PhD1,3; 1Benaroya Research Institute at Virginia Mason, Seattle, WA, 2Virginia Mason Medical Center, 3Department of Medicine, University of Washington. RATIONALE: Peanuts proteins comprised of at least 10 allergic components. The contribution to specific immune responses by each component in each individual is not known. Details characterisation of immune response to allergic components of peanut is required to develop suitable immunotherapeutic strategies. METHODS: Pools of 20-mer peptides spanning the entire sequence of Ara h 1, 2, 3, 6, 8 and 9 protein were used to determine T cell reactivity. CD154-based assay was used in an ex vivo approach to assess at a single cell level the peanut allergen-specific CD4+ T cell responses in peanut allergic individuals. Analysis of the frequency, surface marker phenotype and cytokine profile of these cells was performed to study the mechanism involved in peanut allergic inflammation. A correlation between specific immune response to each peanut allergic component and contribution to clinical symptoms was also evaluated. RESULTS: We observed in our study population inter-individual variations in immunogenicity and type of specific CD4+ T cell immune response to peanut allergic components. Differential ability of the allergic individual to respond to peanut allergic allergens appears to be influenced by HLA class II allele polymorphisms. CONCLUSIONS: Ability to identify immunogenicity and type of response elicited by each peanut allergic component appears to be critical to future success in vaccine development against peanut allergy. Understanding the type of cellular response and the role of genetic restriction may allow to target immune response to critical peanut allergen and to uncover the optimal type of cellular immune response necessary for protection.
J ALLERGY CLIN IMMUNOL FEBRUARY 2013
694
Serum Periostin Levels Correlate with Bronchial Hyperresponsiveness to Mannitol and Methacholine in Children with Asthma Heysung Baek, MD, PhD1, Jae-Won Oh, MD, PhD, FAAAAI2, Ha-Baik Lee, MD, PhD2, Kenji Izuhara, MD, PhD3; 1Hallym University College of Medicine, Seoul, Korea, 2Hanyang University College of Medicine, Seoul, Korea, 3Saga Medical School, Saga, Japan. RATIONALE: Recently it has been found that periostin, a matricellular protein, is a highly inducible product of IL-4 or IL-13 in lung fibroblasts and is involved in fibrosis of bronchial asthma. Effects of serum periostin on bronchial hyperresponsiveness (BHR) have not yet been demonstrated in the human airway. The aim of this study was to address the relationship between serum periostin and BHR in children with asthma. METHODS: Eighty-three children between the ages of 6 and 15 years were included and comprised the asthmatic group (n 5 54) and healthy control group (n 5 29). We measured fractional exhaled nitric oxide (FENO) and serum periostin levels. We performed mannitol and methacholine provocation challenges. The response to methacholine was expressed as a provocative concentration causing a 20% decrease in FEV1 (PC20). The response to mannitol was expressed as a provocative dose causing a 15% fall in FEV1 (PD15) and the response–dose ratio (RDR). RESULTS: Children with asthma had a significantly higher mean (6 SD) level of periostin than controls (78.59 6 17.43 vs. 70.68 6 14.08 ng/mL; P 5 0.034). The serum periostin levels were significantly correlated with FENO (r 5 0.318, P 5 0.023). Serum periostin levels significantly correlate with methacholine PC20 (r 5 -0.325, P 5 0.047) and mannitol PD15 (r 5 -0.391, P 5 0.027) and RDR mannitol (r 5 0.351, P 5 0.023). CONCLUSIONS: Serum periostin levels were increased in asthmatic children and were related to BHR to methacholine and mannitol.
695
Meta Analysis of Asthma Exacerbation Rates in Pediatric Studies During Asthma Managed Using Fractional Exhaled Nitric Oxide Versus Standard Clinical Parameters Alone Joseph D. Spahn, MD1, Jonathan Malka, MD2, Todd A. Mahr, MD, FAAAAI3, Paul M. Dorinsky, MD4; 1National Jewish Health, Denver, CO, 2Pediatric Associates, Aventura, FL, 3Gundersen Lutheran Medical Center, La Crosse, WI, 4Aerocrine, Inc., Morrisville, NC. RATIONALE: A Cochrane Meta-analysis of fractional exhaled nitric oxide (FeNO) versus standard clinical management was published in 2009 (Petsky et al). The primary endpoint was the number of subjects with asthma exacerbations. However, the rate of asthma exacerbations is considered to be the most appropriate endpoint for assessing exacerbations as it takes into account subjects who have multiple exacerbations. Since the original Cochrane Meta-analysis included this information for only 1 of 3 pediatric asthma management studies, the data was reanalyzed to include all 3 pediatric studies from the Cochrane data set. METHODS: Meta-analysis of asthma exacerbation rates in pediatric studies evaluating asthma managed using FeNO versus standard clinical parameters alone. All three available pediatric studies from the original Cochrane data set were included. The methodology for the analysis of exacerbation rates was the same as for the original Cochrane analyses. RESULTS: Across the 3 studies, there were a total of 393 pediatric subjects in the FeNO management group and 389 subjects in the control management group. Asthma exacerbation rates ranged from 0.18-0.66 and 0.25-0.84 across the FeNO and control management groups, respectively. A meta-analysis of exacerbation rates indicates that the exacerbation rate was significantly reduced in favor of the FeNO-based asthma management in children (mean treatment difference 5 -0.11; 95% CI [-0.21, -0.02]). CONCLUSIONS: The data from this meta-analysis in pediatric subjects with asthma indicates that FeNO guided asthma management is a more effective strategy for managing pediatric asthma than the use of clinical parameters alone.