Effect of anti-IgE therapy on food allergen specific T cell responses in eosinophil associated gastrointestinal disorders
<p>Abstract</p> <p>Background</p> <p>Anti-IgE therapy inhibits mast cell and basophil activation, blocks IgE binding to both FcεRI and CD23 and down regulates FcεRI expression by antigen (Ag) presenting cells (APCs). In addition to its classical role in immediate hypers...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2011-04-01
|
| Series: | Clinical and Molecular Allergy |
| Online Access: | http://www.clinicalmolecularallergy.com/content/9/1/7 |
| _version_ | 1818449567642812416 |
|---|---|
| author | Prussin Calman Yin Yuzhi Foroughi Shabnam Foster Barbara |
| author_facet | Prussin Calman Yin Yuzhi Foroughi Shabnam Foster Barbara |
| author_sort | Prussin Calman |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Anti-IgE therapy inhibits mast cell and basophil activation, blocks IgE binding to both FcεRI and CD23 and down regulates FcεRI expression by antigen (Ag) presenting cells (APCs). In addition to its classical role in immediate hypersensitivity, IgE has been shown <it>in vitro </it>to facilitate Ag presentation of allergens, whereby APC bound IgE preferentially takes up allergens for subsequent processing and presentation. The purpose of this study was to determine whether anti-IgE therapy, by blocking facilitated Ag presentation <it>in vivo</it>, attenuates allergen specific Th2 cell responses.</p> <p>Methods</p> <p>To test this hypothesis, food allergen specific T cell responses were examined during a 16-week clinical trial of omalizumab in nine subjects with eosinophilic gastroenteritis and food sensitization. Allergen specific T cell responses were measured using carboxyfluorescein succinimidyl ester dye dilution coupled with intracellular cytokine staining and polychromatic flow cytometry. Four independent indices of allergen specific T cell response (proliferation, Ag dose response, precursor frequency, and the ratio of Th2:Th1 cytokine expression) were determined.</p> <p>Results</p> <p>Eight of the 9 subjects had measurable food allergen specific responses, with a median proliferation index of 112-fold. Allergen specific T cell proliferation was limited to CD4 T cells, whereas CD8 T cell did not proliferate. Food allergen specific responses were Th2 skewed relative to tetanus specific responses in the same subjects. In contradistinction to the original hypothesis, anti-IgE treatment did not diminish any of the four measured indices of allergen specific T cell response.</p> <p>Conclusions</p> <p>In sum, using multiple indices of T cell function, this study failed to demonstrate that anti-IgE therapy broadly or potently inhibits allergen specific T cell responses. As such, these data do not support a major role for IgE facilitated Ag presentation augmenting allergen specific T cell responses <it>in vivo</it>.</p> <p>Trial registration</p> <p>ClinicalTrials.gov identifier <a href="http://www.clinicaltrials.gov/ct2/show/NCT00084097">NCT00084097</a></p> |
| first_indexed | 2024-12-14T20:37:28Z |
| format | Article |
| id | doaj.art-7ae3c9b08f654b24a1499fb29fcacc64 |
| institution | Directory Open Access Journal |
| issn | 1476-7961 |
| language | English |
| last_indexed | 2024-12-14T20:37:28Z |
| publishDate | 2011-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical and Molecular Allergy |
| spelling | doaj.art-7ae3c9b08f654b24a1499fb29fcacc642022-12-21T22:48:21ZengBMCClinical and Molecular Allergy1476-79612011-04-0191710.1186/1476-7961-9-7Effect of anti-IgE therapy on food allergen specific T cell responses in eosinophil associated gastrointestinal disordersPrussin CalmanYin YuzhiForoughi ShabnamFoster Barbara<p>Abstract</p> <p>Background</p> <p>Anti-IgE therapy inhibits mast cell and basophil activation, blocks IgE binding to both FcεRI and CD23 and down regulates FcεRI expression by antigen (Ag) presenting cells (APCs). In addition to its classical role in immediate hypersensitivity, IgE has been shown <it>in vitro </it>to facilitate Ag presentation of allergens, whereby APC bound IgE preferentially takes up allergens for subsequent processing and presentation. The purpose of this study was to determine whether anti-IgE therapy, by blocking facilitated Ag presentation <it>in vivo</it>, attenuates allergen specific Th2 cell responses.</p> <p>Methods</p> <p>To test this hypothesis, food allergen specific T cell responses were examined during a 16-week clinical trial of omalizumab in nine subjects with eosinophilic gastroenteritis and food sensitization. Allergen specific T cell responses were measured using carboxyfluorescein succinimidyl ester dye dilution coupled with intracellular cytokine staining and polychromatic flow cytometry. Four independent indices of allergen specific T cell response (proliferation, Ag dose response, precursor frequency, and the ratio of Th2:Th1 cytokine expression) were determined.</p> <p>Results</p> <p>Eight of the 9 subjects had measurable food allergen specific responses, with a median proliferation index of 112-fold. Allergen specific T cell proliferation was limited to CD4 T cells, whereas CD8 T cell did not proliferate. Food allergen specific responses were Th2 skewed relative to tetanus specific responses in the same subjects. In contradistinction to the original hypothesis, anti-IgE treatment did not diminish any of the four measured indices of allergen specific T cell response.</p> <p>Conclusions</p> <p>In sum, using multiple indices of T cell function, this study failed to demonstrate that anti-IgE therapy broadly or potently inhibits allergen specific T cell responses. As such, these data do not support a major role for IgE facilitated Ag presentation augmenting allergen specific T cell responses <it>in vivo</it>.</p> <p>Trial registration</p> <p>ClinicalTrials.gov identifier <a href="http://www.clinicaltrials.gov/ct2/show/NCT00084097">NCT00084097</a></p>http://www.clinicalmolecularallergy.com/content/9/1/7 |
| spellingShingle | Prussin Calman Yin Yuzhi Foroughi Shabnam Foster Barbara Effect of anti-IgE therapy on food allergen specific T cell responses in eosinophil associated gastrointestinal disorders Clinical and Molecular Allergy |
| title | Effect of anti-IgE therapy on food allergen specific T cell responses in eosinophil associated gastrointestinal disorders |
| title_full | Effect of anti-IgE therapy on food allergen specific T cell responses in eosinophil associated gastrointestinal disorders |
| title_fullStr | Effect of anti-IgE therapy on food allergen specific T cell responses in eosinophil associated gastrointestinal disorders |
| title_full_unstemmed | Effect of anti-IgE therapy on food allergen specific T cell responses in eosinophil associated gastrointestinal disorders |
| title_short | Effect of anti-IgE therapy on food allergen specific T cell responses in eosinophil associated gastrointestinal disorders |
| title_sort | effect of anti ige therapy on food allergen specific t cell responses in eosinophil associated gastrointestinal disorders |
| url | http://www.clinicalmolecularallergy.com/content/9/1/7 |
| work_keys_str_mv | AT prussincalman effectofantiigetherapyonfoodallergenspecifictcellresponsesineosinophilassociatedgastrointestinaldisorders AT yinyuzhi effectofantiigetherapyonfoodallergenspecifictcellresponsesineosinophilassociatedgastrointestinaldisorders AT foroughishabnam effectofantiigetherapyonfoodallergenspecifictcellresponsesineosinophilassociatedgastrointestinaldisorders AT fosterbarbara effectofantiigetherapyonfoodallergenspecifictcellresponsesineosinophilassociatedgastrointestinaldisorders |