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CD4+ T Cells From Nasal Polyp Explants Contain Abundant Th2 Cells Expressing Functional Interleukin-25 Receptors Together With Th17 Cells
Abstracts AB87
J ALLERGY CLIN IMMUNOL VOLUME 133, NUMBER 2
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305
IL-17 Plays a Major Role In Driving The Recruitment Of B Cells Into Bronchial Tissue Of Asthmatic Patients Dr. S. Al-Muhsen, MD1, Mrs. Mary -Angeline Pureza2, Dr. Qutayba Hamid, MD, PhD, FAAAAI3, Dr. Rabih Halwani, PhD4; 1King Saud University, College of Medicine, Riyadh, Saudi Arabia, 2King Saud University, Riyadh, Saudi Arabia, 3McGill University Health Centre, Montreal, QC, Canada, 4King Saud University, college of Medicine, Riyadh, Saudi Arabia. RATIONALE: B cells play an important role in asthma development mostly via the production of IgE. In this proposal, we hypothesized that IgE is increased in lung tissue of asthmatic patients due to increased infiltration of B cells to this tissue. We also investigated the possible involvement of IL-17 in the migration of B cells to the mucosal surface of the airways. METHODS: We determined the number and pattern of infiltrated B cells into bronchial biopsies from asthmatic versus healthy subjects by staining for B cells marker (CD20) using Immunohistochemistry. Migration of B cells towards Th-17 cytokines were examined using Boyden Chamber migration assay. Mechanism of IL-17 induced B cell migration were tested using MAP kinase inhibitors to determine IL-17 induced MAP kinase pathways involved in this process. RESULTS: The number of CD20 positive cells in asthmatic biopsies was significantly higher than those in healthy subjects. Interestingly, we have also observed an increase in B cells lymph follicle numbers in asthmatic airways compared to healthy subjects. Although B cells were shown to migrate in vitro towards both IL-17A and IL-17F, lower concentrations of IL-17F, compared to IL-17A, were sufficient to induce migration. Blocking IL-17 signaling using either anti-IL-17R antibodies or p38 MAP kinase inhibitors prevented in vitro migration of B cell towards IL-17. CONCLUSIONS: These results indicated that IL-17 might drive the migration of B cells in the lung tissues of asthmatic patients. Activation of p38 MAP kinase seems to be required for IL-17 activity on B cells.
306
A Comparison Of Asthma Prevalence and Severity Among Urban and Rural African American Teenage Youth Dr. Dennis Ownby, MD, FAAAAI1, Dr. Martha Tingen, PhD2, Ms. Suzanne Havstad, MA3, Dr. Jennifer Waller, PhD2, Dr. Christine Cole Johnson, PhD, MPH, FAAAAI3, Dr. Christine L. M. Joseph, PhD3; 1 Division of Allergy-Immunology and Rheumatology, Georgia Health Sciences University, Augusta, GA, 2Georgia Regents University, Augusta, GA, 3Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI. RATIONALE: The high prevalence of asthma in African American (AA) populations residing in urban areas of the United States has attracted major attention and research, yet the prevalence of asthma in rural areas is poorly documented. METHODS: The prevalence of asthma was compared in 7550 youth attending six public high schools in urban, Detroit, MI and in 2523 youth attending four public high schools in rural Georgia (GA) counties. Using the Lung Health Survey, diagnosed asthma was defined as a physician diagnosis and symptoms in the past 12 months while undiagnosed asthma was defined as respiratory symptoms in the past 12 months with no physician diagnosis. Chi-square tests were used to compare prevalence by location. RESULTS: In Detroit, 7235 (95.8%) youth were AA compared to 1514 (60.0%) in GA. Average population density in high school ZIP codes was 5628 people/mi2 in Detroit compared to 45.1 people/mi2 in GA. Prevalence of diagnosed asthma was 20.2% in Detroit and 19.4% in GA. Undiagnosed asthma prevalence was 7.7% in Detroit and 7.5% in GA. Detroit youth with a diagnosis experienced more symptom-days, nights awakened, days needing medication, changed plans, and school missed in the prior 30 days compared to GA counterparts (p<0.005). However, the prevalence of symptoms was similar among the undiagnosed youth. CONCLUSIONS: Among AA youth, asthma prevalence is remarkably similar in urban Detroit and rural GA. For those with diagnosed asthma, symptoms were more commonly reported in the Detroit population, but this pattern was not observed among those with undiagnosed asthma.
SUNDAY
CD4+ T Cells From Nasal Polyp Explants Contain Abundant Th2 Cells Expressing Functional Interleukin-25 Receptors Together With Th17 Cells Mrs. Emily Lam, MSc1, Dr. Harsha H. Kariyawasam, MD, PhD2, Prof. Stephen R. Durham, MA, MD, FRCP3, Ms. Joanne Rimmer, FRCS(ORL-HNS)2, Dr. Valerie J. Lund, MD2, Dr. David Cousins, PhD1, Dr. Stephen Till, MD, PhD1; 1King’s College London, London, United Kingdom, 2Royal National Throat, Nose & Ear Hospital London, University College London, London, United Kingdom, 3Imperial College London, London, United Kingdom. RATIONALE: Chronic rhinosinusitis with nasal polyposis (CRSwNP) in western countries is characterized by eosinophilia and IgE production. Surprisingly the local T cell response in polyposis remains poorly characterized in vitro. We previously showed that T cell phenotypes compartmentalize in the healthy nasal mucosa, emphasizing the importance of studying local responses. We sought to test our hypothesis that the local T cell response in CRSwNP is associated with Th2 and nonTh2 pathogenic effector populations that may represent therapeutic targets. METHODS: Polyp tissue and blood were obtained from patients undergoing nasal polypectomy. Healthy nasal biopsies were obtained as controls. Tissue was cultured in an explant model and surface phenotype/intracellular cytokines assessed by flow cytometry and/or immunostaining. RESULTS: Polyp-derived cells contained a discrete population of IL25R+CD4+ T cells, which were not present in peripheral T cells or controls (polyp mean 5 18.8% vs. blood 1.9% (n512; p50.001), vs. healthy biopsy 2.4% (n57; p50.002). IL-25R+CD4+ cells expressed IL-5 and IL-13 that was increased by IL-25 addition. Immunohistochemistry suggested the predominant source of IL-25 in polyps to be epithelial cells. Polyp- and biopsy-derived but not peripheral cells contained significant CD4+CCR6+IL17+ T cells, consistent with Th17 cells. CONCLUSIONS: This is the first demonstration of human explant-derived IL-25R+CD4+ Th2 cells obtained directly from tissue with eosinophilic inflammation. IL-25R is functional since these cells respond to IL-25 in vitro with augmented Th2 cytokine production. The presence of putative Th17 cells in polyp and healthy nasal mucosa suggests that these cells may represent the default T effector phenotype in normal nasal mucosal immunity. Successful Desensitization To Paclitaxel For Stage 4 Ovarian Cancer Dr. Erica T. Gastelum, MD1, Kush Das2, Dr. Praveen Buddiga, MD, FAAAAI3, Dr. Malik N. Baz, MD4; 1UCSF Fresno, Madera, CA, 2Baz Allergy, Asthma & Sinus Center, Fresno, CA, 3University of California San Francisco-Fresno, Fresno, CA; Baz Allergy Asthma & Sinus Center, Fresno, CA, 4UCSF-Fresno, Fresno, CA; Baz Allergy Asthma and Sinus Center, Fresno, CA. RATIONALE: Paclitaxel is a taxane chemotherapeutic agent that has a rare side effect of hypersensitivity reactions. We describe our experience with an effective desensitization protocol following an anaphylactic reaction in a 66 year-old female patient with stage 4 ovarian cancer. METHODS: A patient was unable to complete chemotherapy after developing anaphylaxis on 2 prior cycles of paclitaxel, and was referred to an allergist consultant. Premedication prior to desensitization included dexamethasone, diphenhydramine, and famotidine were administered 13 hours, 7 hours, and 1 hour prior to the infusion of 250 mg of Paclitaxel to our patient who was monitored in the intensive care unit. Divided doses of Paclitaxel were given in 1:100000, 1:10000, 1:1000, 1:100, and 1:10 graded dilutions and infused over 3 hours. Post-medication was provided with dexamethasone and an oral prednisone taper to prevent biphasic sequellae RESULTS: The patient tolerated the desensitization protocol well with the premedication of dexamethasone + diphenhydramine + famotidine. The graded dilutional desensitization approach infused over 3 hours allowed the patient to achieve tolerance to the drug without any significant adverse events and resume her cycles with paclitaxel. CONCLUSIONS: This protocol of graded desensitization in a closely monitored setting permits the continuation of life sustaining antineoplastic treatment protocols in patients that have varying degrees of hypersensitivity to paclitaxel.
J ALLERGY CLIN IMMUNOL VOLUME 133, NUMBER 2
303
304
305
IL-17 Plays a Major Role In Driving The Recruitment Of B Cells Into Bronchial Tissue Of Asthmatic Patients Dr. S. Al-Muhsen, MD1, Mrs. Mary -Angeline Pureza2, Dr. Qutayba Hamid, MD, PhD, FAAAAI3, Dr. Rabih Halwani, PhD4; 1King Saud University, College of Medicine, Riyadh, Saudi Arabia, 2King Saud University, Riyadh, Saudi Arabia, 3McGill University Health Centre, Montreal, QC, Canada, 4King Saud University, college of Medicine, Riyadh, Saudi Arabia. RATIONALE: B cells play an important role in asthma development mostly via the production of IgE. In this proposal, we hypothesized that IgE is increased in lung tissue of asthmatic patients due to increased infiltration of B cells to this tissue. We also investigated the possible involvement of IL-17 in the migration of B cells to the mucosal surface of the airways. METHODS: We determined the number and pattern of infiltrated B cells into bronchial biopsies from asthmatic versus healthy subjects by staining for B cells marker (CD20) using Immunohistochemistry. Migration of B cells towards Th-17 cytokines were examined using Boyden Chamber migration assay. Mechanism of IL-17 induced B cell migration were tested using MAP kinase inhibitors to determine IL-17 induced MAP kinase pathways involved in this process. RESULTS: The number of CD20 positive cells in asthmatic biopsies was significantly higher than those in healthy subjects. Interestingly, we have also observed an increase in B cells lymph follicle numbers in asthmatic airways compared to healthy subjects. Although B cells were shown to migrate in vitro towards both IL-17A and IL-17F, lower concentrations of IL-17F, compared to IL-17A, were sufficient to induce migration. Blocking IL-17 signaling using either anti-IL-17R antibodies or p38 MAP kinase inhibitors prevented in vitro migration of B cell towards IL-17. CONCLUSIONS: These results indicated that IL-17 might drive the migration of B cells in the lung tissues of asthmatic patients. Activation of p38 MAP kinase seems to be required for IL-17 activity on B cells.
306
A Comparison Of Asthma Prevalence and Severity Among Urban and Rural African American Teenage Youth Dr. Dennis Ownby, MD, FAAAAI1, Dr. Martha Tingen, PhD2, Ms. Suzanne Havstad, MA3, Dr. Jennifer Waller, PhD2, Dr. Christine Cole Johnson, PhD, MPH, FAAAAI3, Dr. Christine L. M. Joseph, PhD3; 1 Division of Allergy-Immunology and Rheumatology, Georgia Health Sciences University, Augusta, GA, 2Georgia Regents University, Augusta, GA, 3Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI. RATIONALE: The high prevalence of asthma in African American (AA) populations residing in urban areas of the United States has attracted major attention and research, yet the prevalence of asthma in rural areas is poorly documented. METHODS: The prevalence of asthma was compared in 7550 youth attending six public high schools in urban, Detroit, MI and in 2523 youth attending four public high schools in rural Georgia (GA) counties. Using the Lung Health Survey, diagnosed asthma was defined as a physician diagnosis and symptoms in the past 12 months while undiagnosed asthma was defined as respiratory symptoms in the past 12 months with no physician diagnosis. Chi-square tests were used to compare prevalence by location. RESULTS: In Detroit, 7235 (95.8%) youth were AA compared to 1514 (60.0%) in GA. Average population density in high school ZIP codes was 5628 people/mi2 in Detroit compared to 45.1 people/mi2 in GA. Prevalence of diagnosed asthma was 20.2% in Detroit and 19.4% in GA. Undiagnosed asthma prevalence was 7.7% in Detroit and 7.5% in GA. Detroit youth with a diagnosis experienced more symptom-days, nights awakened, days needing medication, changed plans, and school missed in the prior 30 days compared to GA counterparts (p<0.005). However, the prevalence of symptoms was similar among the undiagnosed youth. CONCLUSIONS: Among AA youth, asthma prevalence is remarkably similar in urban Detroit and rural GA. For those with diagnosed asthma, symptoms were more commonly reported in the Detroit population, but this pattern was not observed among those with undiagnosed asthma.
SUNDAY
CD4+ T Cells From Nasal Polyp Explants Contain Abundant Th2 Cells Expressing Functional Interleukin-25 Receptors Together With Th17 Cells Mrs. Emily Lam, MSc1, Dr. Harsha H. Kariyawasam, MD, PhD2, Prof. Stephen R. Durham, MA, MD, FRCP3, Ms. Joanne Rimmer, FRCS(ORL-HNS)2, Dr. Valerie J. Lund, MD2, Dr. David Cousins, PhD1, Dr. Stephen Till, MD, PhD1; 1King’s College London, London, United Kingdom, 2Royal National Throat, Nose & Ear Hospital London, University College London, London, United Kingdom, 3Imperial College London, London, United Kingdom. RATIONALE: Chronic rhinosinusitis with nasal polyposis (CRSwNP) in western countries is characterized by eosinophilia and IgE production. Surprisingly the local T cell response in polyposis remains poorly characterized in vitro. We previously showed that T cell phenotypes compartmentalize in the healthy nasal mucosa, emphasizing the importance of studying local responses. We sought to test our hypothesis that the local T cell response in CRSwNP is associated with Th2 and nonTh2 pathogenic effector populations that may represent therapeutic targets. METHODS: Polyp tissue and blood were obtained from patients undergoing nasal polypectomy. Healthy nasal biopsies were obtained as controls. Tissue was cultured in an explant model and surface phenotype/intracellular cytokines assessed by flow cytometry and/or immunostaining. RESULTS: Polyp-derived cells contained a discrete population of IL25R+CD4+ T cells, which were not present in peripheral T cells or controls (polyp mean 5 18.8% vs. blood 1.9% (n512; p50.001), vs. healthy biopsy 2.4% (n57; p50.002). IL-25R+CD4+ cells expressed IL-5 and IL-13 that was increased by IL-25 addition. Immunohistochemistry suggested the predominant source of IL-25 in polyps to be epithelial cells. Polyp- and biopsy-derived but not peripheral cells contained significant CD4+CCR6+IL17+ T cells, consistent with Th17 cells. CONCLUSIONS: This is the first demonstration of human explant-derived IL-25R+CD4+ Th2 cells obtained directly from tissue with eosinophilic inflammation. IL-25R is functional since these cells respond to IL-25 in vitro with augmented Th2 cytokine production. The presence of putative Th17 cells in polyp and healthy nasal mucosa suggests that these cells may represent the default T effector phenotype in normal nasal mucosal immunity. Successful Desensitization To Paclitaxel For Stage 4 Ovarian Cancer Dr. Erica T. Gastelum, MD1, Kush Das2, Dr. Praveen Buddiga, MD, FAAAAI3, Dr. Malik N. Baz, MD4; 1UCSF Fresno, Madera, CA, 2Baz Allergy, Asthma & Sinus Center, Fresno, CA, 3University of California San Francisco-Fresno, Fresno, CA; Baz Allergy Asthma & Sinus Center, Fresno, CA, 4UCSF-Fresno, Fresno, CA; Baz Allergy Asthma and Sinus Center, Fresno, CA. RATIONALE: Paclitaxel is a taxane chemotherapeutic agent that has a rare side effect of hypersensitivity reactions. We describe our experience with an effective desensitization protocol following an anaphylactic reaction in a 66 year-old female patient with stage 4 ovarian cancer. METHODS: A patient was unable to complete chemotherapy after developing anaphylaxis on 2 prior cycles of paclitaxel, and was referred to an allergist consultant. Premedication prior to desensitization included dexamethasone, diphenhydramine, and famotidine were administered 13 hours, 7 hours, and 1 hour prior to the infusion of 250 mg of Paclitaxel to our patient who was monitored in the intensive care unit. Divided doses of Paclitaxel were given in 1:100000, 1:10000, 1:1000, 1:100, and 1:10 graded dilutions and infused over 3 hours. Post-medication was provided with dexamethasone and an oral prednisone taper to prevent biphasic sequellae RESULTS: The patient tolerated the desensitization protocol well with the premedication of dexamethasone + diphenhydramine + famotidine. The graded dilutional desensitization approach infused over 3 hours allowed the patient to achieve tolerance to the drug without any significant adverse events and resume her cycles with paclitaxel. CONCLUSIONS: This protocol of graded desensitization in a closely monitored setting permits the continuation of life sustaining antineoplastic treatment protocols in patients that have varying degrees of hypersensitivity to paclitaxel.