- Email: [email protected]
The role of the high affinity IgE receptor in allergic rhinitis in mice
S56 Abstracts
SATURDAY
Skin Prick Test for Anti-Thymocyte Globulin Does Not Predict Immediate ATG-Related Adverse Events P. L. Lugar1, J. Parrino1, N. Young2, J. Chinen3; 1National Institute of Allergy and Infectious Diseases, NIH/DHHS, Bethesda, MD, 2National Heart, Lung, Blood Institute, NIH/DHHS, Bethesda, MD, 3National Human Genome Research Institute, NIH/DHHS, Bethesda, MD. RATIONALE: The predictive value of skin prick test (SPT) prior to antithymocyte globulin (ATG) administration is unknown. We investigated the frequency of immediate adverse reactions with regard to the results of SPT. METHODS: A chart review was conducted on 85 patients treated with horse ATG for aplastic anemia or myelodysplastic syndromes at the NIH from January 2002 to February 2004. ATG SPT was performed prior to treatment. Desensitization was performed in 4 patients with positive or inconclusive SPT. All patients received ATG 40 mg/kg daily for 4 days. RESULTS: SPT was negative in 78, positive in 2, and inconclusive in 5 patients. The majority of patients, including 2 of 4 patients desensitized, experienced reactions suggestive of hypersensitivity. These reactions included hives or rash in 53% (45/85), hypotension or chest pain in 41% (35/85), and wheezing, shortness of breath, or hypoxia in 25% (21/85). Reactions were treated symptomatically; 8 patients, all of whom had negative SPT, required ICU transfer. All 85 patients completed the full course of treatment. CONCLUSIONS: Unexpectedly, a significant number of patients with negative SPT results had immediate adverse reactions. SPT appears to be an inappropriate method for predicting the occurrence of these reactions. Prospective studies need to be conducted to determine if these immediate reactions are IgE-mediated.
224
Production of Th2-, Th1-, and Regulatory Cytokines in Allergic Rhinitis M. Wagenmann, A. Chaker, K. Scheckenbach; ENT-Department, Heinrich-Heine-University Düsseldorf, Düsseldorf, GERMANY. RATIONALE: The type and amount of inflammation characterizing allergic rhinitis is regulated by cytokines. Therefore we investigated the production of Th2 cytokines (IL-4, IL-5, IL-13), Th1 cytokines (IFN-, IL-12), and the regulatory cytokine IL-10 that is potentially capable of downregulating their synthesis. METHODS: Lower turbinate specimen from 23 patients with symptomatic allergic rhinitis in season were included in this study and compared with lower turbinates from 21 nonallergic patients. Single cell suspensions were prepared from the surgical material and analyzed with specific ELISPOT-assays to determine the number of cytokine producing cells. RESULTS: The production of IL-4, IL-5, and IL-13 was significantly elevated in allergics compared to controls (IL-4: 103±24 vs. 70±33 producing cells/100,000 cells, p=0.04; IL-5: 56±25 vs. 13±7, p=0.04; IL-13: 2879±1085 vs. 656±416, p=0.04 (mean±SEM, Wilcoxon-test)). Levels of IL-12 (45±20 vs. 7±2, p=0.02) and IFN- (102±36 vs. 32±16, p=0.01) were also significantly higher in allergics. The number of IL10 producing cells was increased as well (190±59 vs. 44±28, p=0.01). Positive correlations (R>0.6) were found between IL-4 and IL-5, IL12, IL-13; between IL-5 and IL-12, IFN-; between IFN- and IL-10, IL-12. CONCLUSIONS: Our investigation of cytokine production in natural allergic disease demonstrates that the synthesis of both Th2- and Th1cytokines is increased in allergic rhinitis. Analysis of correlations argues against a dichotomy between Th1- and Th2-cytokines - their interaction seems to be more complex. IL-10 is not associated with a downregulation of proinflammatory cytokines in this context. This points to a preponderance of proinflammatory mechanisms or to the relevance of other regulatory mechanisms. Funding: Heinrich-Heine-University Düsseldorf
225
J ALLERGY CLIN IMMUNOL FEBRUARY 2005
Expression of Cysteinyl Leukotriene (Cys-LT) Receptors 1 and 2 in the Nasal Mucosa in Perennial Allergic and Non-Allergic Rhinosinusitis X. Q. Wu1, A. C. Myers1, C. J. Reynolds1, A. C. Goldstone2, A. Togias1, A. M. Sanico1; 1Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, 2Otolaryngology, Johns Hopkins University School of Medicine, Baltimore, MD. RATIONALE: Cys-LTs released from pro-inflammatory cells can produce mucosal changes through at least two receptors (CysLTR-1 or CysLTR-2). We investigated the expression of these receptors in allergic versus non-allergic rhinosinusitis. METHODS: Sections of nasal mucosa obtained from 10 individuals with chronic rhinosinusitis who underwent partial turbinectomy were used for immunofluorescence studies with CysLTR-1 and CysLTR-2 antibodies. Major Cys-LT producing cells, eosinophils and mast cells, were counted using H & E and Giemsa stains. Five subjects had perennial allergic (PAR) and 5 non-allergic rhinosinusitis (NAR) based on history and skin testing. RESULTS: We found more eosinophils along the basement membrane of PAR subjects vs. NAR (mean ± SEM: 52 ± 25 vs. 7 ± 2 per mm2, p=0.03), but mast cells were not different. Immunoreactivity for CysLTR-1 and CysLTR-2 was notable to variable extents on the vascular endothelium of both subject groups. In PAR, we found a higher percentage of vessels with immunoreactivity along the entire vascular circumference for CysLTR-1, compared to CysLTR-2 (23 ± 8 vs. 8 ± 4 %, p=0.04). Comparison of PAR to NAR did not yield differences in the vascular expression of either receptor. CysLTR-1 and CysLTR-2 were also localized on unidentified nasal interstitial cells and glands. Light CysLTR-2 immunofluorescence was noted on epithelial cells. CONCLUSIONS: Cys-LT receptors are found in several elements of the human nasal mucosa in PAR and NAR. In PAR, CysLTR-1 shows stronger vascular expression than CysLTR-2. These findings may impact our understanding of the role of Cys-LTs in rhinosinusitis. Funding: Merck and Co.
226
The Role of the High Affinity IgE Receptor in Allergic Rhinitis in Mice S. Miyahara, N. Miyahara, K. Takeda, S. Matsubara, E. W. Gelfand; Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO. RATIONALE: To define the role of the high affinity IgE receptor (FceRI) in the development of early and late nasal responses to allergen in an allergic rhinitis model in mice. METHODS: Mice with a disruption of the a subunit of the high affinity IgE receptor (FceRI-/-) (BALB/c background) and wild type mice were sensitized to OVA by intraperitoneal injection and then challenged intranasally with OVA, without sedation to ensure no lower airway access to allergen. Nasal responsiveness to OVA was monitored by changes in respiratory pattern and nasal resistance. Histological sections of the nasal tissues were examined. RESULTS: OVA sensitized wild type mice showed an early nasal response to OVA after three daily OVA challenges, whereas sensitized and challenged FceRI-/- mice did not show this early response. Both sensitized wild type mice and FceRI-/- mice exhibited late nasal responses at 6 hours after OVA challenge. Sensitized FceRI-/- mice showed increases in nasal resistance and eosinophilic infiltration compared to challenged only mice, but the responses were lower than observed in sensitized and challenged wild type mice. CONCLUSIONS: These data indicate that FceRI is essential to development of an early nasal response and contributes to development of the late nasal response and eosinophilic infiltration in a mouse model of allergic rhinitis. Funding: NIH grants HL-61005, HL-36577, and EPA grant R825702
227
SATURDAY
Skin Prick Test for Anti-Thymocyte Globulin Does Not Predict Immediate ATG-Related Adverse Events P. L. Lugar1, J. Parrino1, N. Young2, J. Chinen3; 1National Institute of Allergy and Infectious Diseases, NIH/DHHS, Bethesda, MD, 2National Heart, Lung, Blood Institute, NIH/DHHS, Bethesda, MD, 3National Human Genome Research Institute, NIH/DHHS, Bethesda, MD. RATIONALE: The predictive value of skin prick test (SPT) prior to antithymocyte globulin (ATG) administration is unknown. We investigated the frequency of immediate adverse reactions with regard to the results of SPT. METHODS: A chart review was conducted on 85 patients treated with horse ATG for aplastic anemia or myelodysplastic syndromes at the NIH from January 2002 to February 2004. ATG SPT was performed prior to treatment. Desensitization was performed in 4 patients with positive or inconclusive SPT. All patients received ATG 40 mg/kg daily for 4 days. RESULTS: SPT was negative in 78, positive in 2, and inconclusive in 5 patients. The majority of patients, including 2 of 4 patients desensitized, experienced reactions suggestive of hypersensitivity. These reactions included hives or rash in 53% (45/85), hypotension or chest pain in 41% (35/85), and wheezing, shortness of breath, or hypoxia in 25% (21/85). Reactions were treated symptomatically; 8 patients, all of whom had negative SPT, required ICU transfer. All 85 patients completed the full course of treatment. CONCLUSIONS: Unexpectedly, a significant number of patients with negative SPT results had immediate adverse reactions. SPT appears to be an inappropriate method for predicting the occurrence of these reactions. Prospective studies need to be conducted to determine if these immediate reactions are IgE-mediated.
224
Production of Th2-, Th1-, and Regulatory Cytokines in Allergic Rhinitis M. Wagenmann, A. Chaker, K. Scheckenbach; ENT-Department, Heinrich-Heine-University Düsseldorf, Düsseldorf, GERMANY. RATIONALE: The type and amount of inflammation characterizing allergic rhinitis is regulated by cytokines. Therefore we investigated the production of Th2 cytokines (IL-4, IL-5, IL-13), Th1 cytokines (IFN-, IL-12), and the regulatory cytokine IL-10 that is potentially capable of downregulating their synthesis. METHODS: Lower turbinate specimen from 23 patients with symptomatic allergic rhinitis in season were included in this study and compared with lower turbinates from 21 nonallergic patients. Single cell suspensions were prepared from the surgical material and analyzed with specific ELISPOT-assays to determine the number of cytokine producing cells. RESULTS: The production of IL-4, IL-5, and IL-13 was significantly elevated in allergics compared to controls (IL-4: 103±24 vs. 70±33 producing cells/100,000 cells, p=0.04; IL-5: 56±25 vs. 13±7, p=0.04; IL-13: 2879±1085 vs. 656±416, p=0.04 (mean±SEM, Wilcoxon-test)). Levels of IL-12 (45±20 vs. 7±2, p=0.02) and IFN- (102±36 vs. 32±16, p=0.01) were also significantly higher in allergics. The number of IL10 producing cells was increased as well (190±59 vs. 44±28, p=0.01). Positive correlations (R>0.6) were found between IL-4 and IL-5, IL12, IL-13; between IL-5 and IL-12, IFN-; between IFN- and IL-10, IL-12. CONCLUSIONS: Our investigation of cytokine production in natural allergic disease demonstrates that the synthesis of both Th2- and Th1cytokines is increased in allergic rhinitis. Analysis of correlations argues against a dichotomy between Th1- and Th2-cytokines - their interaction seems to be more complex. IL-10 is not associated with a downregulation of proinflammatory cytokines in this context. This points to a preponderance of proinflammatory mechanisms or to the relevance of other regulatory mechanisms. Funding: Heinrich-Heine-University Düsseldorf
225
J ALLERGY CLIN IMMUNOL FEBRUARY 2005
Expression of Cysteinyl Leukotriene (Cys-LT) Receptors 1 and 2 in the Nasal Mucosa in Perennial Allergic and Non-Allergic Rhinosinusitis X. Q. Wu1, A. C. Myers1, C. J. Reynolds1, A. C. Goldstone2, A. Togias1, A. M. Sanico1; 1Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, 2Otolaryngology, Johns Hopkins University School of Medicine, Baltimore, MD. RATIONALE: Cys-LTs released from pro-inflammatory cells can produce mucosal changes through at least two receptors (CysLTR-1 or CysLTR-2). We investigated the expression of these receptors in allergic versus non-allergic rhinosinusitis. METHODS: Sections of nasal mucosa obtained from 10 individuals with chronic rhinosinusitis who underwent partial turbinectomy were used for immunofluorescence studies with CysLTR-1 and CysLTR-2 antibodies. Major Cys-LT producing cells, eosinophils and mast cells, were counted using H & E and Giemsa stains. Five subjects had perennial allergic (PAR) and 5 non-allergic rhinosinusitis (NAR) based on history and skin testing. RESULTS: We found more eosinophils along the basement membrane of PAR subjects vs. NAR (mean ± SEM: 52 ± 25 vs. 7 ± 2 per mm2, p=0.03), but mast cells were not different. Immunoreactivity for CysLTR-1 and CysLTR-2 was notable to variable extents on the vascular endothelium of both subject groups. In PAR, we found a higher percentage of vessels with immunoreactivity along the entire vascular circumference for CysLTR-1, compared to CysLTR-2 (23 ± 8 vs. 8 ± 4 %, p=0.04). Comparison of PAR to NAR did not yield differences in the vascular expression of either receptor. CysLTR-1 and CysLTR-2 were also localized on unidentified nasal interstitial cells and glands. Light CysLTR-2 immunofluorescence was noted on epithelial cells. CONCLUSIONS: Cys-LT receptors are found in several elements of the human nasal mucosa in PAR and NAR. In PAR, CysLTR-1 shows stronger vascular expression than CysLTR-2. These findings may impact our understanding of the role of Cys-LTs in rhinosinusitis. Funding: Merck and Co.
226
The Role of the High Affinity IgE Receptor in Allergic Rhinitis in Mice S. Miyahara, N. Miyahara, K. Takeda, S. Matsubara, E. W. Gelfand; Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO. RATIONALE: To define the role of the high affinity IgE receptor (FceRI) in the development of early and late nasal responses to allergen in an allergic rhinitis model in mice. METHODS: Mice with a disruption of the a subunit of the high affinity IgE receptor (FceRI-/-) (BALB/c background) and wild type mice were sensitized to OVA by intraperitoneal injection and then challenged intranasally with OVA, without sedation to ensure no lower airway access to allergen. Nasal responsiveness to OVA was monitored by changes in respiratory pattern and nasal resistance. Histological sections of the nasal tissues were examined. RESULTS: OVA sensitized wild type mice showed an early nasal response to OVA after three daily OVA challenges, whereas sensitized and challenged FceRI-/- mice did not show this early response. Both sensitized wild type mice and FceRI-/- mice exhibited late nasal responses at 6 hours after OVA challenge. Sensitized FceRI-/- mice showed increases in nasal resistance and eosinophilic infiltration compared to challenged only mice, but the responses were lower than observed in sensitized and challenged wild type mice. CONCLUSIONS: These data indicate that FceRI is essential to development of an early nasal response and contributes to development of the late nasal response and eosinophilic infiltration in a mouse model of allergic rhinitis. Funding: NIH grants HL-61005, HL-36577, and EPA grant R825702
227