- Email: [email protected]
Allergen Challenge Induces Recruitment of CD49d+ Neutrophils to the Nasal Mucosa of Atopic Individuals
AB42 Abstracts
SATURDAY
152
Eosinophils and CD8+ Lymphocytes in the Inflammation and Remodeling Process in Nasal Mucosa in Chinese CRS Patients Wei Zhang, MD1, Leandra Mfuna Endam2, Sawsan Al-Mot2, Ying Li1, Erzhong Fan1, Luo Zhang, MD1, Martin Desrosiers, MD2; 1Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Institute of Otolaryngology, Beijing, China, 2Centre de Recherche du Centre Hospitalier de l’Universite de Montreal (CRCHUM), Montreal, PQ, Canada; Division of Otolaryngology, Centre Hospitalier de l’Universite de Montreal (CHUM), Montreal, PQ, Canada. RATIONALE: Inflammatory cell infiltration and extracellular matrix changes are involved in chronic rhinosinusitis (CRS) disease process. Bacteria play a major role in the underlying etiologies and pathogenesis. We wished to verify whether there was a correlation between bacteria, inflammation and remodeling process. METHODS: Biopsies of the ethmoid bulla were obtained from 12 CRS subjects with nasal polyps (CRSwNP) and 12 CRS without nasal polyps (CRSsNP). 16S rRNA pyrosequencing was performed for bacterial identification followed by microbial composition assessment according to bacterial taxonomy. Inflammatory cells (eosinophils, neutrophils, CD8+ cell) in the mucosa were stained counted and POSTN (representing remodeling in extracellular matrix) were analyzed by immunohistochemistry. The composition of the microbiome on mucosal inflammation and remodeling was also assessed. RESULTS: Gram-negative bacteria (Gr-) predominated in most CRS _5/HPF was subjects (G- 62.7%611.1%, G+ 37.3%611.1%). Eosinophils> seen in half the samples only. Gr-/Gr+ ratio was correlated with CD8+ infiltration (r50.4348). POSTN expression was positively correlated with a high neuutrophil/eosinophil ratio (r50.2363). Comparison of low and high eosinophil groups showed higher expression of POSTN (p50.0341), and lower serum eosinophilia (p50.0139) in neutrophil predominant subjects. CONCLUSIONS: In Chinese CRS patients in China, the microbiome of the sinuses influences CD8+ activity, but not eosinophil or neutrophil populations. It is unknown whether this represents increased responses to Gr– bacteria, or instead whether bacterial factors produced by Gr+ bacteria may suppress inflammation. Neutrophilic predominance in tissue is associated with greater tissue remodeling, however it remains unknown whether neutrophilia increases remodeling or eosinophilia somehow reduces it.
153
Comparison of Allergic Rhinitis Responses During Grass Pollen Season to Those Induced by Controlled Grass Pollen Exposure in the Environmental Exposure Unit (EEU) Emily Kay, MD1, Lisa Steacy, BSc2, Terry Walker, BA2, Barnaby Hobsbawn2, Wilma Hopman, BSc.3, Anne K. Ellis, MD, MSc, FRCPC, FAAAAI2,4; 1Department of Pediatrics, Queen’s University, Kingston, ON, Canada, 2Allergy Research Unit, Kingston General Hospital, Kingston, ON, Canada, 3Clinical Research Unit, Kingston General Hospital, Kingston, ON, Canada, 4Departments of Medicine and Biomedical & Molecular Science, Queen’s University, Kingston, ON, Canada. RATIONALE: The Environmental Exposure Unit (EEU) is a controlled allergen challenge model of allergic rhinitis(AR). We sought to characterize the comparability of symptoms experienced by grass pollen allergic volunteers during the regular grass pollen season to those developed during controlled grass pollen exposure in the EEU. METHODS: Eighteen persons with grass pollen allergy completed mailin surveys in real time during the 2011 grass pollen season, documenting self-perceived AR symptom severity during average and peak pollen exposure days. These same individuals also recorded self-perceived symptom severity while exposed to grass pollen for 3 hours in the EEU. Paired t-tests were used to compare ratings during grass pollen season to the EEU (data averaged over entire 3hr pollen exposure minus baseline). RESULTS: Severity of stuffy nose, runny nose, and itchy/gritty eyes were not significantly different in the EEU from an average grass pollen season day (p 5 0.21, 0.75, 0.17, respectively), while sneezing and watery/red
J ALLERGY CLIN IMMUNOL FEBRUARY 2013
eyes were somewhat less severe in the EEU than that reported during outdoor exposure (p < 0.001 and 0.02, respectively). Similar findings were noted when comparing peak seasonal symptoms to those in the EEU stuffy nose and runny nose were not significantly different, but itchy/gritty eyes, sneezing, and watery/red eyes were significantly less severe in the EEU (p < 0.001 for all). CONCLUSIONS: Most SAR symptoms were of comparable severity during EEU exposure to those experienced in grass pollen season, with sneezing and eye symptoms often less severe in the EEU than noted in the natural season.
154
Allergen Challenge Induces Recruitment of CD49d+ Neutrophils to the Nasal Mucosa of Atopic Individuals Jerome Sigua, MD, Becky Buelow, MD, Meribeth Klancnik, Desire Hunter, Erika Buell, Monica Vasudev, MD, Dorothy S. Cheung, MD, FAAAAI, Mitchell H. Grayson, MD, FAAAAI; Medical College of Wisconsin, Milwaukee, WI. RATIONALE: The mechanism underlying development of atopic disease is unknown. Using a mouse model of post-viral induced atopy, we demonstrated that recruitment of a specific subset of neutrophils (PMN) expressing the integrin CD49d was critical in initiating the atopic response. We undertook this study to see if preferential recruitment of CD49d+ PMN to the nasal mucosa in atopic humans occurred after nasal allergen challenge. METHODS: Atopic and non-atopic adults aged 18-65 were enrolled. After consent a personal atopic history and rhinitis symptom scores were collected. Allergic sensitization was documented by skin testing or serum specific IgE. All subjects underwent a baseline nasal lavage. Atopic subjects were then challenged with either a relevant or irrelevant allergen. Six hours later a nasal lavage was performed. A subsequent challenge with the other allergen (irrelevant or relevant) was performed at least 1 week later. The frequency of CD49d+ PMN in the nasal lavage was determined by flow cytometry. RESULTS: Seven subjects have been enrolled. No CD49d+ PMN were identified in the 3 non-atopic subjects. In atopic subjects (n54), CD49d+ PMN increased only after relevant allergen challenge (1.55+/-1.0% to 6.81+/-3.8%; pre to post challenge mean +/- sem), while with an irrelevant allergen challenge no change was noted (1.09+/-0.5% to 1.52+/-0.5%). CONCLUSIONS: Our preliminary data reveal that CD49d+ PMN are found in the nasal lavage of atopic subjects, and the frequency of these cells can be increased with relevant allergen challenge. These data provide early support that CD49d+ PMN may be associated with development or spread of atopy in humans.
SATURDAY
152
Eosinophils and CD8+ Lymphocytes in the Inflammation and Remodeling Process in Nasal Mucosa in Chinese CRS Patients Wei Zhang, MD1, Leandra Mfuna Endam2, Sawsan Al-Mot2, Ying Li1, Erzhong Fan1, Luo Zhang, MD1, Martin Desrosiers, MD2; 1Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Institute of Otolaryngology, Beijing, China, 2Centre de Recherche du Centre Hospitalier de l’Universite de Montreal (CRCHUM), Montreal, PQ, Canada; Division of Otolaryngology, Centre Hospitalier de l’Universite de Montreal (CHUM), Montreal, PQ, Canada. RATIONALE: Inflammatory cell infiltration and extracellular matrix changes are involved in chronic rhinosinusitis (CRS) disease process. Bacteria play a major role in the underlying etiologies and pathogenesis. We wished to verify whether there was a correlation between bacteria, inflammation and remodeling process. METHODS: Biopsies of the ethmoid bulla were obtained from 12 CRS subjects with nasal polyps (CRSwNP) and 12 CRS without nasal polyps (CRSsNP). 16S rRNA pyrosequencing was performed for bacterial identification followed by microbial composition assessment according to bacterial taxonomy. Inflammatory cells (eosinophils, neutrophils, CD8+ cell) in the mucosa were stained counted and POSTN (representing remodeling in extracellular matrix) were analyzed by immunohistochemistry. The composition of the microbiome on mucosal inflammation and remodeling was also assessed. RESULTS: Gram-negative bacteria (Gr-) predominated in most CRS _5/HPF was subjects (G- 62.7%611.1%, G+ 37.3%611.1%). Eosinophils> seen in half the samples only. Gr-/Gr+ ratio was correlated with CD8+ infiltration (r50.4348). POSTN expression was positively correlated with a high neuutrophil/eosinophil ratio (r50.2363). Comparison of low and high eosinophil groups showed higher expression of POSTN (p50.0341), and lower serum eosinophilia (p50.0139) in neutrophil predominant subjects. CONCLUSIONS: In Chinese CRS patients in China, the microbiome of the sinuses influences CD8+ activity, but not eosinophil or neutrophil populations. It is unknown whether this represents increased responses to Gr– bacteria, or instead whether bacterial factors produced by Gr+ bacteria may suppress inflammation. Neutrophilic predominance in tissue is associated with greater tissue remodeling, however it remains unknown whether neutrophilia increases remodeling or eosinophilia somehow reduces it.
153
Comparison of Allergic Rhinitis Responses During Grass Pollen Season to Those Induced by Controlled Grass Pollen Exposure in the Environmental Exposure Unit (EEU) Emily Kay, MD1, Lisa Steacy, BSc2, Terry Walker, BA2, Barnaby Hobsbawn2, Wilma Hopman, BSc.3, Anne K. Ellis, MD, MSc, FRCPC, FAAAAI2,4; 1Department of Pediatrics, Queen’s University, Kingston, ON, Canada, 2Allergy Research Unit, Kingston General Hospital, Kingston, ON, Canada, 3Clinical Research Unit, Kingston General Hospital, Kingston, ON, Canada, 4Departments of Medicine and Biomedical & Molecular Science, Queen’s University, Kingston, ON, Canada. RATIONALE: The Environmental Exposure Unit (EEU) is a controlled allergen challenge model of allergic rhinitis(AR). We sought to characterize the comparability of symptoms experienced by grass pollen allergic volunteers during the regular grass pollen season to those developed during controlled grass pollen exposure in the EEU. METHODS: Eighteen persons with grass pollen allergy completed mailin surveys in real time during the 2011 grass pollen season, documenting self-perceived AR symptom severity during average and peak pollen exposure days. These same individuals also recorded self-perceived symptom severity while exposed to grass pollen for 3 hours in the EEU. Paired t-tests were used to compare ratings during grass pollen season to the EEU (data averaged over entire 3hr pollen exposure minus baseline). RESULTS: Severity of stuffy nose, runny nose, and itchy/gritty eyes were not significantly different in the EEU from an average grass pollen season day (p 5 0.21, 0.75, 0.17, respectively), while sneezing and watery/red
J ALLERGY CLIN IMMUNOL FEBRUARY 2013
eyes were somewhat less severe in the EEU than that reported during outdoor exposure (p < 0.001 and 0.02, respectively). Similar findings were noted when comparing peak seasonal symptoms to those in the EEU stuffy nose and runny nose were not significantly different, but itchy/gritty eyes, sneezing, and watery/red eyes were significantly less severe in the EEU (p < 0.001 for all). CONCLUSIONS: Most SAR symptoms were of comparable severity during EEU exposure to those experienced in grass pollen season, with sneezing and eye symptoms often less severe in the EEU than noted in the natural season.
154
Allergen Challenge Induces Recruitment of CD49d+ Neutrophils to the Nasal Mucosa of Atopic Individuals Jerome Sigua, MD, Becky Buelow, MD, Meribeth Klancnik, Desire Hunter, Erika Buell, Monica Vasudev, MD, Dorothy S. Cheung, MD, FAAAAI, Mitchell H. Grayson, MD, FAAAAI; Medical College of Wisconsin, Milwaukee, WI. RATIONALE: The mechanism underlying development of atopic disease is unknown. Using a mouse model of post-viral induced atopy, we demonstrated that recruitment of a specific subset of neutrophils (PMN) expressing the integrin CD49d was critical in initiating the atopic response. We undertook this study to see if preferential recruitment of CD49d+ PMN to the nasal mucosa in atopic humans occurred after nasal allergen challenge. METHODS: Atopic and non-atopic adults aged 18-65 were enrolled. After consent a personal atopic history and rhinitis symptom scores were collected. Allergic sensitization was documented by skin testing or serum specific IgE. All subjects underwent a baseline nasal lavage. Atopic subjects were then challenged with either a relevant or irrelevant allergen. Six hours later a nasal lavage was performed. A subsequent challenge with the other allergen (irrelevant or relevant) was performed at least 1 week later. The frequency of CD49d+ PMN in the nasal lavage was determined by flow cytometry. RESULTS: Seven subjects have been enrolled. No CD49d+ PMN were identified in the 3 non-atopic subjects. In atopic subjects (n54), CD49d+ PMN increased only after relevant allergen challenge (1.55+/-1.0% to 6.81+/-3.8%; pre to post challenge mean +/- sem), while with an irrelevant allergen challenge no change was noted (1.09+/-0.5% to 1.52+/-0.5%). CONCLUSIONS: Our preliminary data reveal that CD49d+ PMN are found in the nasal lavage of atopic subjects, and the frequency of these cells can be increased with relevant allergen challenge. These data provide early support that CD49d+ PMN may be associated with development or spread of atopy in humans.