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il-9r-pathway In Murine Systemic And Intestinal Anaphylaxis.
S186 Abstracts
711
The Utility of Serum Tryptase in the Diagnosis of Shrimpinduced Anaphylaxis P. Wongkaewpothong, P. Pacharn, C. Sripramong, S. Boomchoo, N. Visitsunthorn, P. Vichyanond, O. Jirapongsananuruk; Mahidol university, Bangkok, Thailand. RATIONALE: The role of serum tryptase to verify shrimp-induced anaphylaxis has not been determined. The aim was to investigate the utility of serum tryptase for the confirmation of shrimp-induced anaphylaxis. METHODS: Patients with history of shrimp allergy and positive skin tests to shrimp were recruited for shrimp challenges. Serum tryptase was obtained at baseline and 1 hour (peak) after the onset of symptoms. RESULTS: Thirty-nine patients were challenged. There were 12 patients with anaphylaxis (anaphylaxis group), 20 with mild reactions (non-anaphylaxis group), and 7 without symptom (control group). Characteristic features, mean wheal diameter (MWD) of skin prick test with commercial shrimp extract, and baseline tryptase were not different among 3 groups. Anaphylaxis group had greater MWD of prick to prick test than non-anaphylaxis group (15 vs 8.5 mm, p 5 0.01). The peak tryptase levels were higher than baseline in anaphylaxis (2.77 vs 1.24 mg/L) and non-anaphylaxis groups (1.78 vs 1.58 mg/L),(p < 0.05). The delta tryptase (peak minus baseline) values in anaphylaxis group were higher than non-anaphylaxis (1.42 vs 0.16 mg/L, p < 0.01) and control groups (1.42 vs 0.07 mg/L, p < 0.01). The tryptase ratio (peak divided by baseline) values in anaphylaxis group were higher than non-anaphylaxis (2.22 vs 1.10, p < 0.01) and control groups (2.22 vs 1.02, p < 0.01). ROC established the best cutoff of peak tryptase at 2.99 mg/L with 50% sensitivity and 85% specificity, whereas the recommended 12 mg/L cutoff showed 25% sensitivity and 100% specificity. CONCLUSIONS: Serial tryptase values, including tryptase ratio and/or delta tryptase values, are more helpful than peak serum tryptase for the confirmation of food-induced anaphylaxis.
712
MONDAY
Elevated Intestinal Interleukin-13 Promotes Intestinal Epithelial Barrier Dysfunction D. X. Wu1, R. E. Ahrens1, K. R. Groschwitz1, H. N. Osterfield1, P. S. Foster2,3, F. D. Finkelman1,4, K. I. Matthaei2, S. P. Hogan1; 1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2Division of Molecular Bioscience, John Curtin School of Medical Research, Canberra, Australia, 3 School of Biomedical Sciences, University of Newcastle, Newcastle, Australia, 4Department of Medicine, Cincinnati Veterans Affair Medical Center, Cincinnati, OH. RATIONALE: Experimental investigations suggest that Th2-derived cytokines (IL-4, IL-5, IL-9 and IL-13) are central in the induction of the intestinal manifestations of food allergy. To delineate the contribution of IL13 in intestinal dysfunction we generated intestinal IL-13 transgenic mouse (iIL-13Tg). METHODS: Intestinal permeability [mucosal-serosal flux of FITC-dextran and HRP, and inversely correlating transepithelial resistance (TER)] on isolated jejunum segments from WT and iIL-13Tg mice was measured by an Ussing system. Systemic IL-13, IL-13 Ra2/IL13 complex, and % saturation of IL-13Ra2 were determined by ELISA. Intestinal mast cell levels were quantitated by CAE activity. RESULTS: IIL-13Tg mice had increased serum IL-13 (17.580 6 2.325 vs 10.540 6 0.829 ng/ml, p 5 0.0357), and reduced % saturation of IL-13Ra2 (14.24% 6 1.393% vs 24.36% 6 2.639%, p 5 0.0148) as compared to WT mice, Notably, intestinal mast cell levels (7.683 6 3.756 vs 4.267 6 0.3812 mast cells/hpf) were comparable between groups; however iIL13Tg mice had increased intestinal permeability (TER: 70.03 6 4.852 vs 134.2 6 10.64 V * cm2, p 5 0.0006)], transcellular flux of FITC-dextran (5.708 6 1.461 vs 1.663 6 0.565 ng/ml, p < 0.0001) and pararcellular flux of HRP (0.018 6 0.0033 vs 0.005 6 0.001 ng/ml, p < 0.0001). CONCLUSIONS: These data demonstrate that intestinal IL-13 regulates intestinal epithelial cell transcellular and paracellular permeability independent of an intestinal mastocytosis.
J ALLERGY CLIN IMMUNOL FEBRUARY 2009
713
The Effect on Length of Stay of Weekend Compared to Weekday Admission for Anaphylaxis Z. D. Mulla1, M. R. Simon2; 1Texas Tech University HSC, Paul L. Foster School of Medicine, El Paso, TX, 2Wayne State University School of Medicine, Detroit, MI. RATIONALE: Studies have found that patients who were admitted on weekend days fared worse than patients who were admitted on weekdays. However, those investigations did not study patients hospitalized for anaphylaxis. The objective of this study was to determine if there was an association between day of admission for anaphylaxis and the outcome of length of stay (LOS). METHODS: Florida hospital data (year 2001) were analyzed. Patients who had a principal discharge diagnosis of anaphylaxis were identified using ICD-9-CM codes (n 5 458). The risk factor was weekend admission (Friday, Saturday, or Sunday) compared to weekday admission. Due to the skewed nature of LOS, a three-level outcome variable was created: 1, 2, or 3 or more days. Adjusted odds ratios (aOR) were calculated using ordinal logistic regression (cumulative logit). The assumption of proportional odds was met. RESULTS: A total of 173 patients were admitted on the weekend. A trend toward association between admission day (weekend vs. weekday) and LOS was detected (aOR 5 1.39, 95% confidence interval: 0.96-2.03, p 5 0.08). Increasing age was associated with longer LOS (p 5 0.01). Medicaid status, admission quarter, admission to a teaching hospital, race, and asthma were not risk factors for LOS. Men tended to have a shorter LOS than females (aOR 5 0.50, p 5 0.0003). The presence of ischemic heart disease more than doubled the odds of having a longer LOS (aOR 5 2.41, p 5 0.002). Hymenoptera sting anaphylaxis did not affect LOS. CONCLUSIONS: Weekend admission for anaphylaxis was not correlated with LOS. However, a large portion of the confidence interval includes elevated aORs and therefore further investigations are warranted.
714
Dissection Of The Role Of Il-9/il-9r-pathway In Murine Systemic And Intestinal Anaphylaxis. H. N. Osterfeld1, R. Ahrens1, D. Wu1, E. Forbes1, F. Finkelman2, J. Renauld3, S. Hogan1; 1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2Cincinnati VA Medical Center, Cincinnati, OH, 3Ludwig Institute for Cancer Research, Brussels, Belgium. RATIONALE: We have recently demonstrated a critical role for IL-9 in intestinal anaphylaxis. In contrast, previous studies have demonstrated that IL-9 promotes but is not necessary for systemic anaphylaxis. We define the role of IL-9/IL-9R in intestinal and systemic anaphylaxis. METHODS: Experimental intestinal anaphylaxis was induced in WT (BALB/c) IL-9- and IL-9R-deficient mice. Passive IgE- and IgG-mediated systemic anaphylaxis was induced by intra-venous administration of 10 mg anti-IgE and 500 mg anti-IgG. Intestinal anaphylaxis was determined by detection of diarrhea. Systemic anaphylaxis was quantitated by rectal thermometry. Mast cell levels and activation by histology and mast cell protease-1 (mcpt-1) ELISA. RESULTS: Seven i.g. challenges of ovalbumin (OVA) to OVA-sensitized WT mice induced experimental intestinal anaphylaxis [diarrhea (ratio of mice with diarrhea; 4/4); intestinal mastocytosis (mc-hpf; 69.8 6 5.8, n 5 4), serum mcpt-1 (mg/ml; 693.0 6 210.0, n 5 4) and OVA-specific IgE (1.4 1 0.3 O.D. units; n 5 4)]. In contrast, intestinal anaphylaxis was attenuated in IL-9 and IL-9R mice [diarrhea occurrence; 1/6 and 3/ 6; respectively; mc-hpf; 9.4 6 6.0 and 17.9 6 6.7, *p < 0.05 compared to WT mice; n 5 4; mcpt-1 (mg/ml); 11 6 2.9 and 17.0 6 7.6; n 5 4; *p < 0.05). I.v. administration of anti-IgG induced passive systemic anaphylaxis in WT mice as compared to Ig-control treated mice (DTemp8C; 25.5 6 0.9 and -0.8 6 1.0; n 5 11; p < 0.01). Similarly, anti-IgG treatment induced passive systemic anaphylaxis in IL-9 and IL-9R-deficient mice (DTemp8C; -5.3. 6 1.7 and 23.6 6 1.7, n 5 9-11). CONCLUSIONS: Collectively, these data demonstrate that IL-9 is critical for experimental intestinal anaphylaxis but is not essential for systemic anaphylaxis.
711
The Utility of Serum Tryptase in the Diagnosis of Shrimpinduced Anaphylaxis P. Wongkaewpothong, P. Pacharn, C. Sripramong, S. Boomchoo, N. Visitsunthorn, P. Vichyanond, O. Jirapongsananuruk; Mahidol university, Bangkok, Thailand. RATIONALE: The role of serum tryptase to verify shrimp-induced anaphylaxis has not been determined. The aim was to investigate the utility of serum tryptase for the confirmation of shrimp-induced anaphylaxis. METHODS: Patients with history of shrimp allergy and positive skin tests to shrimp were recruited for shrimp challenges. Serum tryptase was obtained at baseline and 1 hour (peak) after the onset of symptoms. RESULTS: Thirty-nine patients were challenged. There were 12 patients with anaphylaxis (anaphylaxis group), 20 with mild reactions (non-anaphylaxis group), and 7 without symptom (control group). Characteristic features, mean wheal diameter (MWD) of skin prick test with commercial shrimp extract, and baseline tryptase were not different among 3 groups. Anaphylaxis group had greater MWD of prick to prick test than non-anaphylaxis group (15 vs 8.5 mm, p 5 0.01). The peak tryptase levels were higher than baseline in anaphylaxis (2.77 vs 1.24 mg/L) and non-anaphylaxis groups (1.78 vs 1.58 mg/L),(p < 0.05). The delta tryptase (peak minus baseline) values in anaphylaxis group were higher than non-anaphylaxis (1.42 vs 0.16 mg/L, p < 0.01) and control groups (1.42 vs 0.07 mg/L, p < 0.01). The tryptase ratio (peak divided by baseline) values in anaphylaxis group were higher than non-anaphylaxis (2.22 vs 1.10, p < 0.01) and control groups (2.22 vs 1.02, p < 0.01). ROC established the best cutoff of peak tryptase at 2.99 mg/L with 50% sensitivity and 85% specificity, whereas the recommended 12 mg/L cutoff showed 25% sensitivity and 100% specificity. CONCLUSIONS: Serial tryptase values, including tryptase ratio and/or delta tryptase values, are more helpful than peak serum tryptase for the confirmation of food-induced anaphylaxis.
712
MONDAY
Elevated Intestinal Interleukin-13 Promotes Intestinal Epithelial Barrier Dysfunction D. X. Wu1, R. E. Ahrens1, K. R. Groschwitz1, H. N. Osterfield1, P. S. Foster2,3, F. D. Finkelman1,4, K. I. Matthaei2, S. P. Hogan1; 1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2Division of Molecular Bioscience, John Curtin School of Medical Research, Canberra, Australia, 3 School of Biomedical Sciences, University of Newcastle, Newcastle, Australia, 4Department of Medicine, Cincinnati Veterans Affair Medical Center, Cincinnati, OH. RATIONALE: Experimental investigations suggest that Th2-derived cytokines (IL-4, IL-5, IL-9 and IL-13) are central in the induction of the intestinal manifestations of food allergy. To delineate the contribution of IL13 in intestinal dysfunction we generated intestinal IL-13 transgenic mouse (iIL-13Tg). METHODS: Intestinal permeability [mucosal-serosal flux of FITC-dextran and HRP, and inversely correlating transepithelial resistance (TER)] on isolated jejunum segments from WT and iIL-13Tg mice was measured by an Ussing system. Systemic IL-13, IL-13 Ra2/IL13 complex, and % saturation of IL-13Ra2 were determined by ELISA. Intestinal mast cell levels were quantitated by CAE activity. RESULTS: IIL-13Tg mice had increased serum IL-13 (17.580 6 2.325 vs 10.540 6 0.829 ng/ml, p 5 0.0357), and reduced % saturation of IL-13Ra2 (14.24% 6 1.393% vs 24.36% 6 2.639%, p 5 0.0148) as compared to WT mice, Notably, intestinal mast cell levels (7.683 6 3.756 vs 4.267 6 0.3812 mast cells/hpf) were comparable between groups; however iIL13Tg mice had increased intestinal permeability (TER: 70.03 6 4.852 vs 134.2 6 10.64 V * cm2, p 5 0.0006)], transcellular flux of FITC-dextran (5.708 6 1.461 vs 1.663 6 0.565 ng/ml, p < 0.0001) and pararcellular flux of HRP (0.018 6 0.0033 vs 0.005 6 0.001 ng/ml, p < 0.0001). CONCLUSIONS: These data demonstrate that intestinal IL-13 regulates intestinal epithelial cell transcellular and paracellular permeability independent of an intestinal mastocytosis.
J ALLERGY CLIN IMMUNOL FEBRUARY 2009
713
The Effect on Length of Stay of Weekend Compared to Weekday Admission for Anaphylaxis Z. D. Mulla1, M. R. Simon2; 1Texas Tech University HSC, Paul L. Foster School of Medicine, El Paso, TX, 2Wayne State University School of Medicine, Detroit, MI. RATIONALE: Studies have found that patients who were admitted on weekend days fared worse than patients who were admitted on weekdays. However, those investigations did not study patients hospitalized for anaphylaxis. The objective of this study was to determine if there was an association between day of admission for anaphylaxis and the outcome of length of stay (LOS). METHODS: Florida hospital data (year 2001) were analyzed. Patients who had a principal discharge diagnosis of anaphylaxis were identified using ICD-9-CM codes (n 5 458). The risk factor was weekend admission (Friday, Saturday, or Sunday) compared to weekday admission. Due to the skewed nature of LOS, a three-level outcome variable was created: 1, 2, or 3 or more days. Adjusted odds ratios (aOR) were calculated using ordinal logistic regression (cumulative logit). The assumption of proportional odds was met. RESULTS: A total of 173 patients were admitted on the weekend. A trend toward association between admission day (weekend vs. weekday) and LOS was detected (aOR 5 1.39, 95% confidence interval: 0.96-2.03, p 5 0.08). Increasing age was associated with longer LOS (p 5 0.01). Medicaid status, admission quarter, admission to a teaching hospital, race, and asthma were not risk factors for LOS. Men tended to have a shorter LOS than females (aOR 5 0.50, p 5 0.0003). The presence of ischemic heart disease more than doubled the odds of having a longer LOS (aOR 5 2.41, p 5 0.002). Hymenoptera sting anaphylaxis did not affect LOS. CONCLUSIONS: Weekend admission for anaphylaxis was not correlated with LOS. However, a large portion of the confidence interval includes elevated aORs and therefore further investigations are warranted.
714
Dissection Of The Role Of Il-9/il-9r-pathway In Murine Systemic And Intestinal Anaphylaxis. H. N. Osterfeld1, R. Ahrens1, D. Wu1, E. Forbes1, F. Finkelman2, J. Renauld3, S. Hogan1; 1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2Cincinnati VA Medical Center, Cincinnati, OH, 3Ludwig Institute for Cancer Research, Brussels, Belgium. RATIONALE: We have recently demonstrated a critical role for IL-9 in intestinal anaphylaxis. In contrast, previous studies have demonstrated that IL-9 promotes but is not necessary for systemic anaphylaxis. We define the role of IL-9/IL-9R in intestinal and systemic anaphylaxis. METHODS: Experimental intestinal anaphylaxis was induced in WT (BALB/c) IL-9- and IL-9R-deficient mice. Passive IgE- and IgG-mediated systemic anaphylaxis was induced by intra-venous administration of 10 mg anti-IgE and 500 mg anti-IgG. Intestinal anaphylaxis was determined by detection of diarrhea. Systemic anaphylaxis was quantitated by rectal thermometry. Mast cell levels and activation by histology and mast cell protease-1 (mcpt-1) ELISA. RESULTS: Seven i.g. challenges of ovalbumin (OVA) to OVA-sensitized WT mice induced experimental intestinal anaphylaxis [diarrhea (ratio of mice with diarrhea; 4/4); intestinal mastocytosis (mc-hpf; 69.8 6 5.8, n 5 4), serum mcpt-1 (mg/ml; 693.0 6 210.0, n 5 4) and OVA-specific IgE (1.4 1 0.3 O.D. units; n 5 4)]. In contrast, intestinal anaphylaxis was attenuated in IL-9 and IL-9R mice [diarrhea occurrence; 1/6 and 3/ 6; respectively; mc-hpf; 9.4 6 6.0 and 17.9 6 6.7, *p < 0.05 compared to WT mice; n 5 4; mcpt-1 (mg/ml); 11 6 2.9 and 17.0 6 7.6; n 5 4; *p < 0.05). I.v. administration of anti-IgG induced passive systemic anaphylaxis in WT mice as compared to Ig-control treated mice (DTemp8C; 25.5 6 0.9 and -0.8 6 1.0; n 5 11; p < 0.01). Similarly, anti-IgG treatment induced passive systemic anaphylaxis in IL-9 and IL-9R-deficient mice (DTemp8C; -5.3. 6 1.7 and 23.6 6 1.7, n 5 9-11). CONCLUSIONS: Collectively, these data demonstrate that IL-9 is critical for experimental intestinal anaphylaxis but is not essential for systemic anaphylaxis.