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Oral immunotherapy induces local protective mechanisms in the gastrointestinal mucosa  Stephanie A. Leonard, MD, Gustavo Martos, PhD, Wei Wang, MD, Anna.

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Presentation on theme: "Oral immunotherapy induces local protective mechanisms in the gastrointestinal mucosa  Stephanie A. Leonard, MD, Gustavo Martos, PhD, Wei Wang, MD, Anna."— Presentation transcript:

1 Oral immunotherapy induces local protective mechanisms in the gastrointestinal mucosa 
Stephanie A. Leonard, MD, Gustavo Martos, PhD, Wei Wang, MD, Anna Nowak-Węgrzyn, MD, M. Cecilia Berin, PhD  Journal of Allergy and Clinical Immunology  Volume 129, Issue 6, Pages e1 (June 2012) DOI: /j.jaci Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 OIT results in desensitization but not tolerance to OVA (A) or OM (B). OVA- and OM-sensitized mice were administered OIT, or left untreated (control). Mice were orally challenged (on OIT), and again 2 weeks after the discontinuation of OIT (off OIT). Thirty minutes after the challenge, body temperature was measured (left) and a clinical score was assigned (right). ns, Not significant. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Immunologic changes associated with OIT in mice. Mice were orally sensitized to OVA, followed by the administration of egg white OIT. A, OVA-specific IgE, IgG1, IgG2a, and IgA levels measured in serum obtained on the last day of OIT. B, Cytokine secretion from OVA-restimulated spleen cells obtained 2 weeks after OIT discontinuation. *P < .05. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 OIT decreases gastrointestinal epithelial barrier function. Mice were orally sensitized to OVA, followed by the administration of egg white OIT on days 0 to 14. On day 15, segments of jejunum were removed and mounted in Ussing chambers. Transmural resistance was measured at baseline (left), and luminal-to-serosal transport of FITC-dextran was measured over a 90-minute period (right). FITC, Fluorescein isothiocyanate. **P < .01. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 High-dose OIT is required for clinical protection against OVA-induced anaphylaxis in sensitized mice. OVA-sensitized mice were administered high-dose or low-dose fresh egg white OIT on days 0 to 14, or left untreated (control). Mice were orally challenged on day 15. Thirty minutes after the challenge, body temperature was measured (left) and a clinical score was assigned (right). Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Extensively heated OM protects mice against anaphylaxis. OM-sensitized mice were administered native or heated-OM OIT on days 0 to 14, or left untreated (control). Mice were orally challenged with native OM on day 15. Thirty minutes after the challenge, body temperature was measured (left) and a clinical score was assigned (right). Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 6 Clinical protection is localized to the gastrointestinal tract. OVA-sensitized mice received egg white OIT on days 0 to 14. On day 15: A, Peripheral blood basophil activation. *P < .05 versus naive. B, Peritoneal mast cell activation. n = 5 per group. **P < .01 versus unstimulated. C, Body temperature before and after the challenge. D, Body temperature after graded intraperitoneal dose challenge to OVA. MFI, Median fluorescence intensity. ∗∗∗P < .001 versus naive. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig 7 OIT significantly alters intestinal gene expression. A, Jejunal gene expression of pancreatic lipase (Pnlp), trypsin 4 (Try4), trypsin 5 (Try5), and GP2 was measured by PCR. B, Expression of Pnlp and Try4 in proximal and mid duodenum, jejunum, and proximal and distal ileum. Expression of Pnlp and Try4 in isolated intestinal epithelial cells (IEC) compared with full-thickness intestine (right). CT, Cholera toxin; GAPDH, Glyceraldehyde 3-phosphate dehydrogenase. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Fig E1 A, Basophil activation as measured by CD200R. Whole blood was incubated in plates coated with anti-IgE (R35-72) or rat IgG1 as isotype control, or with 10 μg of OVA. Cells were stained, and basophils identified as CD3neg CD19neg CD49bpos IgEpos. Left: CD200R expression on basophils incubated with media alone (shaded histogram), isotype control (solid line), or anti-IgE (dotted line). Right: Basophils from naive, OVA-sensitized but untreated (control), or OVA-sensitized and OIT-treated (OIT) mice, incubated with media alone (shaded histogram) or OVA (solid line). Histograms are representative of 3 individual experiments, with each experiment using pooled blood from 3 to 4 mice per group. B, Peritoneal mast cell activation as measured by LAMP-1. Top panel: Peritoneal cells were harvested from naive mice and incubated in plates coated with anti-IgE (R35-72) or rat IgG1 as isotype control. Cells were harvested after 30, 60, or 120 minutes, and LAMP-1 detected on c-kitpos FcεRIpos cells. Data from 3 individual mice are shown in the graph on the right. Bottom panel: Peritoneal cells were harvested from naive, control, or OIT-treated mice and cultured with OVA (10 μg) or media alone for 60 minutes. LAMP-1 was then detected as above. Histograms are representative of 5 mice per group. MFI, Median fluorescence intensity. Journal of Allergy and Clinical Immunology  , e1DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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