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Psychosocial Functioning in Children and Adolescents with Eosinophilic Esophagitis (EoE) and Their Families
AB106 Abstracts
397
SUNDAY
Peanut Allergen Exposure Promotes Eosinophilic Esophagitis (EE) In Mice M. Rayapudi, P. Rajaveylu, S. Narayanan, A. Mishra; Cincinnati Children’s Hospital, Cincinnati, OH. RATIONALE: EE is a recently recognized esophageal inflammatory disease and food allergens are believed to be a major cause of the disease progression in pediatric and adult patients. However, yet not proven that EE is a food allergen-induced disease. In an attempt to establish that food allergens promote EE, we examined a number of food allergens that have hypersensitivity in EE patients. Interestingly, patient data set indicates that peanut and corn hypersensitivity is most common in human EE; therefore, we tested the hypothesis whether peanut and corn allergens are an effective inducer of EE. METHODS: Mice were sensitized and exposed either intranasally or intragastrically with corn or peanut extract or saline. Esophageal eosinophilia, eosinophil active genes and immunoglobulin antibodies were examined by performing anti-MBP-immunostaining, qPCR and ELISA analysis, respectively. RESULTS: We observed number of EE characteristics, such as eosinophilic microabscesses, intraepithelial eosinophils, extracellular eosinophilc granules, thickened and disrupted epithelial mucosa and mast cells accumulation in the esopgagus of peanut-induced experimental EE in mice. The eosinophil numbers in the esophagus of intranasal and intragastric peanut-challenged mice were 63.9641.9/mm2 and 19.564.5/mm2 compared to 11.9612.5 /mm2 and 7.1366.8/mm2 in saline-challenged mice. Additionally, serum IgE and eosinophil active cytokine genes (IL5 and IL-13) in the esophagus were elevated following peanut-challenge in mice. Notably, the magnitude of esophageal eosinophilia in peanut-challenged mice was significantly higher than corn-challenged mice. CONCLUSION: Taken together, we first time report that peanut-allergens are effective inducers of experimental EE and induce high number of esophageal eosinophilia compared to corn-allergen.
398
Psychosocial Functioning in Children and Adolescents with Eosinophilic Esophagitis (EoE) and Their Families R. F. Harris1, N. Riechers1, G. T. Furuta2, D. Atkins1, M. D. Klinnert1; 1 National Jewish Health, Denver, CO, 2The Children’s Hospital, Aurora, CO. RATIONALE: Children with EoE face multiple psychosocial challenges. The psychological impact of living with this chronic disease is unknown. We describe psychosocial difficulties that were documented among children and their families referred for psychosocial evaluation. METHODS: Chart reviews were conducted for 93 patients who attended a clinic for EGID evaluation and received a psychosocial assessment by a psychologist or social worker. Reports were reviewed and rated for depression, anxiety, social functioning difficulties, sleep problems, overall psychological adjustment, and family coping. RESULTS: Patients were 1-18 yrs (x57.2, SD54.7), 78% male, and 91% from intact families. Diagnoses included EoE (60%), undiagnosed (26%), no EoE (12%), and other EGID (2%). Among children age 5 and older, 31% evidenced depression, 45% anxiety, and 19% social functioning difficulties. Children without diagnosis or with EoE ruled out were more likely to evidence depression than those with an EoE diagnosis (p<0.05). Sleep difficulties were present in 18% of the sample; 44% had adjustment difficulties. Child adjustment problems increased with age (p50.003). Coping difficulties were noted in 47% of families; families of children age 0-4 had more difficulties coping than of children ages 8-18 (p<0.05). There was no difference between diagnostic groups in terms of psychological adjustment and family coping. CONCLUSIONS: Children referred to a tertiary care center for EGID evaluation have psychological and coping difficulties. Increased attention should be paid to this co-morbid aspect of these diseases. Future studies should incorporate standardized assessment instruments along with clinician judgment to determine the nature of support required for these children and their families.
J ALLERGY CLIN IMMUNOL FEBRUARY 2011
399
The Pan-B Cell Marker CD22 (siglec 2) Is Expressed On Gastro-intestinal (GI) Eosinophils And Negatively Regulates GI Eosinophil Survival T. Wen1, C. Blanchard1, B. Wahl2, O. Pabst2, M. E. Rothenberg1; 1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2Institute of Immunology, Hannover Medical School, Hannover, GERMANY. RATIONALE: We aimed to identify tissue specific markers that could distinguish eosinophils in different tissues and explore their functions. METHODS: Eosinophils were purified from multiple tissues by FACS and RNA was subjected to genome-wide expression profile analysis. In order to confirm the mRNA array at a protein level, we developed a FACSbased protocol to phenotype murine GI eosinophils isolated from the lamina propria. RESULTS: Herein, tissue specific eosinophil mRNA microarray analysis identifies CD22 transcripts on gastrointestinal (GI) eosinophils with levels 10-fold higher than lung eosinophils. Jejunum eosinophils expressed remarkably high level of surface CD22 across multiple mouse strains. In contrast, CD22 was undetectable on eosinophils from the colon, blood, thymus, spleen, uterus, peritoneal cavity and allergen challenged lung. Eosinophils isolated from newborn mice did not express CD22, but subsequently upregulated CD22 to adult level within the first 10 days after birth. Yet, germ free adult mice had normal CD22 expression, suggesting little role for GI bacteria in regulating CD22 expression. CD2-IL-5 transgenic had reduced CD22 expression on GI eosinophils, indicating that systemic elevation of IL-5 inhibits GI eosinophil expression of CD22. In CD22-/mice, jejunum eosinophil density was 30% higher compared to wild-type mice, as shown by both FACS analysis and MBP1 morphometric quantification. After collagenase facilitated isolation, CD22-/- GI eosinophils had a higher rate of cell death and increased pSAPK activation compared with wild-type eosinophils. CONCLUSIONS: CD22 is highly expressed on GI eosinophils and negatively regulates GI eosinophil survival, suggesting a modulatory role of CD22 on GI eosinophil function in mucosal responses.
400
Allergic Component of Adult Eosinophilic Esophagitis K. N. Cahill1, J. Sheikh2; 1Brigham and Women’s Hospital, Boston, MA, 2Beth Israel Deaconess Medical Center, Boston, MA. RATIONALE: Current knowledge of allergen-mediated adult eosinophilic esophagitis (EoE) is limited to a few case reports and retrospective case series. The roles of food and aeroallergen sensitization in the pathogenesis of adult EoE remain uncertain. METHODS: Charts were selected from January 2004 through December 2009 by billing codes for EoE (ICD-9 530.13), or the combination of eosinophilia (ICD-9 288.3) and esophagitis (ICD-9 530.11). Subjects’ food and environmental skin prick testing (SPT) and ImmunoCAP specific IgE results were reviewed. RESULTS: Chart review revealed 93 patients meeting EoE diagnostic criteria. A personal history of atopy was reported in 74%, most often allergic rhinitis (70%) and asthma (27%), and 55% reported a family history of at_1 food sensitizations were identified in 78% (n569) with a opy. On SPT, > _1 aeroallergen sensitizations were identified mean of 7.6 positive tests and > in 75% (n520) with a mean of 10.5 positive tests. The most common food sensitizations were peanut or soy (58%), tree nuts (57%), wheat or rye (36%), and corn (30%). The most common aeroallergen sensitizations were trees (75%) and grasses (65%). Rates of sensitization were compared with those of the general population as determined from the NHANES III and 2005-6 studies. CONCLUSIONS: Tree nuts, peanut, soy, corn, and rye or wheat are the most common food sensitizations and trees and grasses are the most common environmental sensitizations detected in adult EoE patients. This data supports a role for food and aeroallergen sensitization in the pathogenesis of adult EoE.
397
SUNDAY
Peanut Allergen Exposure Promotes Eosinophilic Esophagitis (EE) In Mice M. Rayapudi, P. Rajaveylu, S. Narayanan, A. Mishra; Cincinnati Children’s Hospital, Cincinnati, OH. RATIONALE: EE is a recently recognized esophageal inflammatory disease and food allergens are believed to be a major cause of the disease progression in pediatric and adult patients. However, yet not proven that EE is a food allergen-induced disease. In an attempt to establish that food allergens promote EE, we examined a number of food allergens that have hypersensitivity in EE patients. Interestingly, patient data set indicates that peanut and corn hypersensitivity is most common in human EE; therefore, we tested the hypothesis whether peanut and corn allergens are an effective inducer of EE. METHODS: Mice were sensitized and exposed either intranasally or intragastrically with corn or peanut extract or saline. Esophageal eosinophilia, eosinophil active genes and immunoglobulin antibodies were examined by performing anti-MBP-immunostaining, qPCR and ELISA analysis, respectively. RESULTS: We observed number of EE characteristics, such as eosinophilic microabscesses, intraepithelial eosinophils, extracellular eosinophilc granules, thickened and disrupted epithelial mucosa and mast cells accumulation in the esopgagus of peanut-induced experimental EE in mice. The eosinophil numbers in the esophagus of intranasal and intragastric peanut-challenged mice were 63.9641.9/mm2 and 19.564.5/mm2 compared to 11.9612.5 /mm2 and 7.1366.8/mm2 in saline-challenged mice. Additionally, serum IgE and eosinophil active cytokine genes (IL5 and IL-13) in the esophagus were elevated following peanut-challenge in mice. Notably, the magnitude of esophageal eosinophilia in peanut-challenged mice was significantly higher than corn-challenged mice. CONCLUSION: Taken together, we first time report that peanut-allergens are effective inducers of experimental EE and induce high number of esophageal eosinophilia compared to corn-allergen.
398
Psychosocial Functioning in Children and Adolescents with Eosinophilic Esophagitis (EoE) and Their Families R. F. Harris1, N. Riechers1, G. T. Furuta2, D. Atkins1, M. D. Klinnert1; 1 National Jewish Health, Denver, CO, 2The Children’s Hospital, Aurora, CO. RATIONALE: Children with EoE face multiple psychosocial challenges. The psychological impact of living with this chronic disease is unknown. We describe psychosocial difficulties that were documented among children and their families referred for psychosocial evaluation. METHODS: Chart reviews were conducted for 93 patients who attended a clinic for EGID evaluation and received a psychosocial assessment by a psychologist or social worker. Reports were reviewed and rated for depression, anxiety, social functioning difficulties, sleep problems, overall psychological adjustment, and family coping. RESULTS: Patients were 1-18 yrs (x57.2, SD54.7), 78% male, and 91% from intact families. Diagnoses included EoE (60%), undiagnosed (26%), no EoE (12%), and other EGID (2%). Among children age 5 and older, 31% evidenced depression, 45% anxiety, and 19% social functioning difficulties. Children without diagnosis or with EoE ruled out were more likely to evidence depression than those with an EoE diagnosis (p<0.05). Sleep difficulties were present in 18% of the sample; 44% had adjustment difficulties. Child adjustment problems increased with age (p50.003). Coping difficulties were noted in 47% of families; families of children age 0-4 had more difficulties coping than of children ages 8-18 (p<0.05). There was no difference between diagnostic groups in terms of psychological adjustment and family coping. CONCLUSIONS: Children referred to a tertiary care center for EGID evaluation have psychological and coping difficulties. Increased attention should be paid to this co-morbid aspect of these diseases. Future studies should incorporate standardized assessment instruments along with clinician judgment to determine the nature of support required for these children and their families.
J ALLERGY CLIN IMMUNOL FEBRUARY 2011
399
The Pan-B Cell Marker CD22 (siglec 2) Is Expressed On Gastro-intestinal (GI) Eosinophils And Negatively Regulates GI Eosinophil Survival T. Wen1, C. Blanchard1, B. Wahl2, O. Pabst2, M. E. Rothenberg1; 1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2Institute of Immunology, Hannover Medical School, Hannover, GERMANY. RATIONALE: We aimed to identify tissue specific markers that could distinguish eosinophils in different tissues and explore their functions. METHODS: Eosinophils were purified from multiple tissues by FACS and RNA was subjected to genome-wide expression profile analysis. In order to confirm the mRNA array at a protein level, we developed a FACSbased protocol to phenotype murine GI eosinophils isolated from the lamina propria. RESULTS: Herein, tissue specific eosinophil mRNA microarray analysis identifies CD22 transcripts on gastrointestinal (GI) eosinophils with levels 10-fold higher than lung eosinophils. Jejunum eosinophils expressed remarkably high level of surface CD22 across multiple mouse strains. In contrast, CD22 was undetectable on eosinophils from the colon, blood, thymus, spleen, uterus, peritoneal cavity and allergen challenged lung. Eosinophils isolated from newborn mice did not express CD22, but subsequently upregulated CD22 to adult level within the first 10 days after birth. Yet, germ free adult mice had normal CD22 expression, suggesting little role for GI bacteria in regulating CD22 expression. CD2-IL-5 transgenic had reduced CD22 expression on GI eosinophils, indicating that systemic elevation of IL-5 inhibits GI eosinophil expression of CD22. In CD22-/mice, jejunum eosinophil density was 30% higher compared to wild-type mice, as shown by both FACS analysis and MBP1 morphometric quantification. After collagenase facilitated isolation, CD22-/- GI eosinophils had a higher rate of cell death and increased pSAPK activation compared with wild-type eosinophils. CONCLUSIONS: CD22 is highly expressed on GI eosinophils and negatively regulates GI eosinophil survival, suggesting a modulatory role of CD22 on GI eosinophil function in mucosal responses.
400
Allergic Component of Adult Eosinophilic Esophagitis K. N. Cahill1, J. Sheikh2; 1Brigham and Women’s Hospital, Boston, MA, 2Beth Israel Deaconess Medical Center, Boston, MA. RATIONALE: Current knowledge of allergen-mediated adult eosinophilic esophagitis (EoE) is limited to a few case reports and retrospective case series. The roles of food and aeroallergen sensitization in the pathogenesis of adult EoE remain uncertain. METHODS: Charts were selected from January 2004 through December 2009 by billing codes for EoE (ICD-9 530.13), or the combination of eosinophilia (ICD-9 288.3) and esophagitis (ICD-9 530.11). Subjects’ food and environmental skin prick testing (SPT) and ImmunoCAP specific IgE results were reviewed. RESULTS: Chart review revealed 93 patients meeting EoE diagnostic criteria. A personal history of atopy was reported in 74%, most often allergic rhinitis (70%) and asthma (27%), and 55% reported a family history of at_1 food sensitizations were identified in 78% (n569) with a opy. On SPT, > _1 aeroallergen sensitizations were identified mean of 7.6 positive tests and > in 75% (n520) with a mean of 10.5 positive tests. The most common food sensitizations were peanut or soy (58%), tree nuts (57%), wheat or rye (36%), and corn (30%). The most common aeroallergen sensitizations were trees (75%) and grasses (65%). Rates of sensitization were compared with those of the general population as determined from the NHANES III and 2005-6 studies. CONCLUSIONS: Tree nuts, peanut, soy, corn, and rye or wheat are the most common food sensitizations and trees and grasses are the most common environmental sensitizations detected in adult EoE patients. This data supports a role for food and aeroallergen sensitization in the pathogenesis of adult EoE.