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Risk Factor for Asthma Severity in Children: Family History, Atopic Sensitization or Rhinitis
S100 Abstracts
Risk Factor for Asthma Severity in Children: Family History, Atopic Sensitization or Rhinitis H. L. B. S. Santos1, L. G. Möller1, N. P. Duarte, Jr.1, R. Morihisa1, C. A. Riedi2, N. A. Rosario2; 1Hospital de Clinicas - Universidade Federal do Paraná, Curitiba, BRAZIL, 2Pediatric Immunology and Pneumology, Hospital de Clinicas - Universidade Federal do Paraná, Curitiba, BRAZIL. RATIONALE: We assessed important risk factors (sensitization, family history or rhinitis) for the development of asthma severity in children. METHODS: Chart review of patients with persistent asthma attending on outpatient allergy clinic. Skin prick test (SPT) were performed with common local inhalant allergens and were considered positive if wheal size was > 3mm greater than control. Parental history was considered positive if father mother or sibling had a consistent history of atopic disease (asthma, rhinitis and eczema).Asthma severity and rhinitis diagnosis were considered according to GINA and ARIA protocols. RESULTS: From 2000 - 2004, 831 outpatients were worked-up for asthma (mild = 320 [38,5%], moderate = 452 [54,5%] and severe = 59 [7,0%]). SPT was performed in 700 patients, of these, 146 (52,9%) , 229(61,4%) and 32 (62,7%) respectively had positive result to at least one of the allergens tested (p<0,01). Family history was positive for 186 (58,1%), 283 (62,6%), 35 (59,3%) respectively for mild, moderated and severe asthma. (p>0,05) The presence of rhinitis was observed in 237 (74,1%) with mild asthma, 372 (82,3%) with moderated and 52 (88.1%) with severe asthma (p<0,005). CONCLUSIONS: Moderate asthma was the most frequent presentation in this population sample. Rhinitis and atopic sensitization were risk factors associated with asthma severity. In contrast, family history did not show association with severity of asthma.
389
SUNDAY
390
Lung Features of Infection with Corona Virus in Wistar Rats
M. T. Glocker1, H. Cabaral1, J. C. Muiño2; 1Instituto de Biología Celular, Facultad de Ciencias Médicas - Universidad Nacional de Córdoba, Cordoba, ARGENTINA, 2Medicina III - UHMI N 4, Facultad de Ciencias Médicas Universidad Nacional de Córdoba, Cordoba, ARGENTINA. RATIONALE: The immune spectrum of severe acute respiratory syndrome (SARS) is poorly understood. Our purpose was to study the dynamics of the immune spectrum in respiratory Corona Virus (Co V) infection trough nasal cavity. METHODS: 12 animals were infected and compared with 14 normal healthy animals. We assayed in both groups the serum IgM, IgG, IgA and C 3 levels by RID, specific IgG to Co V by ELISA, CD 3, CD 4, CD 8 lymphocytes by IF. Lung histophatological study was performed in all rats by Mo anti Co V and biotin-steptavidin alkaline phosphatase label-fast red. RESULTS: Following the evolution, 10 of 12 rats with Co V died in the following 60 days and the rest of rats of the control group survival, p<0.0001. The IgM, IgG , IgA and C 3 levels were increases in Co V group when compared with controls, p<0.0001. The specific IgG to Co V was positive in 12 of 12 cases Co V inoculation and negative in 14 normal rats, p< 0.0001. CD 3, CD 4 and CD 8 cells decreased significantly in acute phase when compared with normal group, p<0.0001. Histophatological changes of interstitial pneumonia were found at death. Positive immunostaining for Co V was found in all infected rats. Control cases were negative. CONCLUSIONS: The Co V elicited humoral immunity but inhibited cellular immunity, and the lung showed positive Co V corpuscles in the epithelial cells. Funding: Grant of Secyt UNC Influence of Il-4 on Prostaglandin and Leukotriene Metabolic Pathways E. B. Barekzi1, J. W. Steinke1, R. Caughey2, L. Borish1; 1Asthma and Allergic Diseases Center, University of Virginia, Charlottesville, VA, 2Otolaryngology, University of Virginia, Charlottesville, VA.
391
J ALLERGY CLIN IMMUNOL FEBRUARY 2006
RATIONALE: Prostaglandin E2 and leukotrienes can have opposite effects on bronchial hyperreactivity and inflammation. IL-4 is a key cytokine involved in allergic inflammation that increases expression of the leukotriene receptors and, in mast cells, the enzyme leukotriene C4 synthase (LTC4S). These studies examined the effect of IL-4 on expression of enzymes in the prostaglandin and leukotriene synthesis pathways in monocytes and eosinophils. METHODS: Monocytes and eosinophils were isolated from peripheral blood by magnetic affinity selection. We compared data from unstimulated to IL-4-stimulated cells. Changes in mRNA expression (quantitative PCR) of prostaglandin E2 synthase (PGES), cyclooxygenase (Cox)-2, LTC4S and 5-lipoxygenase (5-LO) and protein levels (ELISA) of PGE2 and Cox 2 were measured. RESULTS: Lipopolysaccharide and IL-1beta-stimulated Cox-2 and PGES mRNA expression in monocytes. Basal and stimulated expression of these genes were inhibited by IL-4. In contrast to mast cells, IL-4 inhibited expression of LTC4S and 5-LO expression. IL-4 inhibited Cox-2 and PGES mRNA expression in eosinophils, while 5-LO expression was increased. LTC4S expression was unchanged by IL-4 in eosinophils. CONCLUSIONS: Our results suggest that IL-4 can shift the products of the arachadonic acid pathway from the protective prostaglandin PGE2 to the inflammatory leukotrienes. Inhibiting PGES and Cox-2 in monocytes and eosinophils along with increased 5-LO expression in eosinophils will push arachadonic acid metabolites towards leukotriene production. Higher levels of leukotrienes can lead to increases in bronchial hyperreactivity and asthma exacerbations in susceptible individuals and could predispose patients to aspirin intolerance. Funding: NIH Transgenic Mice Expressing Catalytically Inactive RAG-1 Exhibit Hypogammaglobulinemia and Altered B Cell Development, but not Autoreactivity K. W. Parks1, A. E. Hassaballa2, D. K. Anderson2, Q. Hu3, T. B. Casale1, P. C. Swanson2,1; 1Allergy and Immunology, Creighton University, Omaha, NE, 2Medical Microbiology and Immunology, Creighton University, Omaha, NE, 3Pathology, Creighton University, Omaha, NE. RATIONALE: To test whether over-expression of a catalytically inactive form of RAG-1 (recombination activating gene) in mice could disrupt B cell maturation, impair B cell receptor editing, and promote autoimmune disease. METHODS: Transgenic RAG-1 mice with active site mutations blocking catalytic activity but not DNA-binding capacity were examined for serum immunoglobulin concentrations and anti-nuclear antibodies (ANA) by ELISA. Primary and secondary lymphoid tissues from age-matched paired littermates were evaluated by H & E staining and immunohistochemistry. RESULTS: Previous flow cytometric analyses demonstrate that transgenic RAG-1 mice accumulate B220loCD19+ B cells that phenotypically resemble B1 B cells. Here we find that immunoglobulin levels (g/ml) are reduced in transgenic animals as compared to age-matched littermates (mean IgG 443 versus 1330, p=0.012; IgM 85 versus 261, p=0.005). After correcting for absolute IgG concentration, ANA optical density measurements did not differ significantly (p=0.10). Immunohistochemical staining revealed a reduction in B220+ cells around splenic lymphoid follicles but no difference in CD19+ cells. No evident histologic changes were observed in H & E-stained tissue sections of spleen, lymph node, or thymus of transgenic versus normal mice. CONCLUSIONS: Transgenic RAG-1 mice accumulate B1-like B cells, yet exhibit hypogammaglobulinemia. We speculate that if receptor editing is impaired by transgene overexpression, B1-like B cells accumulate but fail to differentiate into plasma cells, reducing natural immunoglobulin levels. This model system should be helpful in elucidating the role of RAG-1 in normal and impaired B cell responses associated with immunodeficiencies and autoimmune disorders. Funding: LB692 Nebraska Tobacco Settlement Biomedical Research Program
392
Risk Factor for Asthma Severity in Children: Family History, Atopic Sensitization or Rhinitis H. L. B. S. Santos1, L. G. Möller1, N. P. Duarte, Jr.1, R. Morihisa1, C. A. Riedi2, N. A. Rosario2; 1Hospital de Clinicas - Universidade Federal do Paraná, Curitiba, BRAZIL, 2Pediatric Immunology and Pneumology, Hospital de Clinicas - Universidade Federal do Paraná, Curitiba, BRAZIL. RATIONALE: We assessed important risk factors (sensitization, family history or rhinitis) for the development of asthma severity in children. METHODS: Chart review of patients with persistent asthma attending on outpatient allergy clinic. Skin prick test (SPT) were performed with common local inhalant allergens and were considered positive if wheal size was > 3mm greater than control. Parental history was considered positive if father mother or sibling had a consistent history of atopic disease (asthma, rhinitis and eczema).Asthma severity and rhinitis diagnosis were considered according to GINA and ARIA protocols. RESULTS: From 2000 - 2004, 831 outpatients were worked-up for asthma (mild = 320 [38,5%], moderate = 452 [54,5%] and severe = 59 [7,0%]). SPT was performed in 700 patients, of these, 146 (52,9%) , 229(61,4%) and 32 (62,7%) respectively had positive result to at least one of the allergens tested (p<0,01). Family history was positive for 186 (58,1%), 283 (62,6%), 35 (59,3%) respectively for mild, moderated and severe asthma. (p>0,05) The presence of rhinitis was observed in 237 (74,1%) with mild asthma, 372 (82,3%) with moderated and 52 (88.1%) with severe asthma (p<0,005). CONCLUSIONS: Moderate asthma was the most frequent presentation in this population sample. Rhinitis and atopic sensitization were risk factors associated with asthma severity. In contrast, family history did not show association with severity of asthma.
389
SUNDAY
390
Lung Features of Infection with Corona Virus in Wistar Rats
M. T. Glocker1, H. Cabaral1, J. C. Muiño2; 1Instituto de Biología Celular, Facultad de Ciencias Médicas - Universidad Nacional de Córdoba, Cordoba, ARGENTINA, 2Medicina III - UHMI N 4, Facultad de Ciencias Médicas Universidad Nacional de Córdoba, Cordoba, ARGENTINA. RATIONALE: The immune spectrum of severe acute respiratory syndrome (SARS) is poorly understood. Our purpose was to study the dynamics of the immune spectrum in respiratory Corona Virus (Co V) infection trough nasal cavity. METHODS: 12 animals were infected and compared with 14 normal healthy animals. We assayed in both groups the serum IgM, IgG, IgA and C 3 levels by RID, specific IgG to Co V by ELISA, CD 3, CD 4, CD 8 lymphocytes by IF. Lung histophatological study was performed in all rats by Mo anti Co V and biotin-steptavidin alkaline phosphatase label-fast red. RESULTS: Following the evolution, 10 of 12 rats with Co V died in the following 60 days and the rest of rats of the control group survival, p<0.0001. The IgM, IgG , IgA and C 3 levels were increases in Co V group when compared with controls, p<0.0001. The specific IgG to Co V was positive in 12 of 12 cases Co V inoculation and negative in 14 normal rats, p< 0.0001. CD 3, CD 4 and CD 8 cells decreased significantly in acute phase when compared with normal group, p<0.0001. Histophatological changes of interstitial pneumonia were found at death. Positive immunostaining for Co V was found in all infected rats. Control cases were negative. CONCLUSIONS: The Co V elicited humoral immunity but inhibited cellular immunity, and the lung showed positive Co V corpuscles in the epithelial cells. Funding: Grant of Secyt UNC Influence of Il-4 on Prostaglandin and Leukotriene Metabolic Pathways E. B. Barekzi1, J. W. Steinke1, R. Caughey2, L. Borish1; 1Asthma and Allergic Diseases Center, University of Virginia, Charlottesville, VA, 2Otolaryngology, University of Virginia, Charlottesville, VA.
391
J ALLERGY CLIN IMMUNOL FEBRUARY 2006
RATIONALE: Prostaglandin E2 and leukotrienes can have opposite effects on bronchial hyperreactivity and inflammation. IL-4 is a key cytokine involved in allergic inflammation that increases expression of the leukotriene receptors and, in mast cells, the enzyme leukotriene C4 synthase (LTC4S). These studies examined the effect of IL-4 on expression of enzymes in the prostaglandin and leukotriene synthesis pathways in monocytes and eosinophils. METHODS: Monocytes and eosinophils were isolated from peripheral blood by magnetic affinity selection. We compared data from unstimulated to IL-4-stimulated cells. Changes in mRNA expression (quantitative PCR) of prostaglandin E2 synthase (PGES), cyclooxygenase (Cox)-2, LTC4S and 5-lipoxygenase (5-LO) and protein levels (ELISA) of PGE2 and Cox 2 were measured. RESULTS: Lipopolysaccharide and IL-1beta-stimulated Cox-2 and PGES mRNA expression in monocytes. Basal and stimulated expression of these genes were inhibited by IL-4. In contrast to mast cells, IL-4 inhibited expression of LTC4S and 5-LO expression. IL-4 inhibited Cox-2 and PGES mRNA expression in eosinophils, while 5-LO expression was increased. LTC4S expression was unchanged by IL-4 in eosinophils. CONCLUSIONS: Our results suggest that IL-4 can shift the products of the arachadonic acid pathway from the protective prostaglandin PGE2 to the inflammatory leukotrienes. Inhibiting PGES and Cox-2 in monocytes and eosinophils along with increased 5-LO expression in eosinophils will push arachadonic acid metabolites towards leukotriene production. Higher levels of leukotrienes can lead to increases in bronchial hyperreactivity and asthma exacerbations in susceptible individuals and could predispose patients to aspirin intolerance. Funding: NIH Transgenic Mice Expressing Catalytically Inactive RAG-1 Exhibit Hypogammaglobulinemia and Altered B Cell Development, but not Autoreactivity K. W. Parks1, A. E. Hassaballa2, D. K. Anderson2, Q. Hu3, T. B. Casale1, P. C. Swanson2,1; 1Allergy and Immunology, Creighton University, Omaha, NE, 2Medical Microbiology and Immunology, Creighton University, Omaha, NE, 3Pathology, Creighton University, Omaha, NE. RATIONALE: To test whether over-expression of a catalytically inactive form of RAG-1 (recombination activating gene) in mice could disrupt B cell maturation, impair B cell receptor editing, and promote autoimmune disease. METHODS: Transgenic RAG-1 mice with active site mutations blocking catalytic activity but not DNA-binding capacity were examined for serum immunoglobulin concentrations and anti-nuclear antibodies (ANA) by ELISA. Primary and secondary lymphoid tissues from age-matched paired littermates were evaluated by H & E staining and immunohistochemistry. RESULTS: Previous flow cytometric analyses demonstrate that transgenic RAG-1 mice accumulate B220loCD19+ B cells that phenotypically resemble B1 B cells. Here we find that immunoglobulin levels (g/ml) are reduced in transgenic animals as compared to age-matched littermates (mean IgG 443 versus 1330, p=0.012; IgM 85 versus 261, p=0.005). After correcting for absolute IgG concentration, ANA optical density measurements did not differ significantly (p=0.10). Immunohistochemical staining revealed a reduction in B220+ cells around splenic lymphoid follicles but no difference in CD19+ cells. No evident histologic changes were observed in H & E-stained tissue sections of spleen, lymph node, or thymus of transgenic versus normal mice. CONCLUSIONS: Transgenic RAG-1 mice accumulate B1-like B cells, yet exhibit hypogammaglobulinemia. We speculate that if receptor editing is impaired by transgene overexpression, B1-like B cells accumulate but fail to differentiate into plasma cells, reducing natural immunoglobulin levels. This model system should be helpful in elucidating the role of RAG-1 in normal and impaired B cell responses associated with immunodeficiencies and autoimmune disorders. Funding: LB692 Nebraska Tobacco Settlement Biomedical Research Program
392