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11. Nitration of ovalbumin decreases the risk for sensitization via the oral route in a mouse food allergy model

Author

Diesner Susanne C, Untersmayr Eva, Oostingh Gertie J, Selzle Kathrin, Pfaller Tobias, Schultz Cornelia, Zhang Yingyi, Krishnamurthy Durga, Starkl Philipp, Knittelfelder Regina, Förster-Waldl Elisabeth, Pollak Arnold, Scheiner Otto, Pöschl Ulrich, Jensen-Jarolim Erika, and Duschl Albert

Subjects
Immunologic diseases. Allergy, RC581-607
Published
2011
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30. Anaphylaxis to Russian Beluga caviar

Author

Untersmayr, Eva, Focke, Margit, Kinaciyan, Tamar, Poulsen, Lars K., Boltz-Nitulescu, George, Scheiner, Otto, and Jensen-Jarolim, Erika

Published
2002

47. Specificity of Mimotope-Induced Anti-High Molecular Weight-Melanoma Associated Antigen (HMW-MAA) Antibodies Does Not Ensure Biological Activity.

Author

Latzka, Julia, Gaier, Sonja, Hofstetter, Gerlinde, Balazs, Nina, Smole, Ursula, Ferrone, Soldano, Scheiner, Otto, Breiteneder, Heimo, Pehamberger, Hubert, and Wagner, Stefan

Subjects
MELANOMA, VACCINES, ANTIGENS, MOLECULAR weights, NEUROBLASTOMA
Abstract

Vaccines based on peptide mimics (mimotopes) of conformational tumor antigen epitopes have been investigated for a variety of human tumors including breast cancer, tumors expressing the carcinoembryonic antigen, B cell lymphoma, neuroblastoma, and melanoma. In our previous work, we designed a vaccine based on a mimotope of the high molecular weight-melanoma associated antigen (HMW-MAA) that elicited HMW-MAA-specific antibodies (Abs) with anti-tumor activity in vitro and in vivo. In this study, we aimed to identify mimotopes of additional distinct HMW-MAA epitopes, since they could be used to construct a polymimotope melanoma vaccine. For this purpose, random peptide phage libraries were screened with the anti-HMW-MAA monoclonal antibodies (mAbs) VT80.12 and VF1-TP43 yielding one peptide ligand for each mAb. Both peptides inhibited the binding of the corresponding mAb to the HMW-MAA. Furthermore, when coupled to the carrier protein keyhole limpet hemocyanin (KLH), both HMW-MAA mimotopes elicited peptide-specific Abs in rabbits or BALB/c mice, but only the mimotope isolated with the mAb VT80.12 elicited HMW-MAA-specific Abs and only in mice. However, the latter Abs had no detectable effect on HMW-MAA expressing human melanoma cells in vitro. These results describe limitations related to the phage display technique and emphasize the need to characterize the functional properties of the mAb utilized to isolate mimotopes of the corresponding epitopes. [ABSTRACT FROM AUTHOR]

Published
2011
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48. Nitration of the Egg-Allergen Ovalbumin Enhances Protein Allergenicity but Reduces the Risk for Oral Sensitization in a Murine Model of Food Allergy.

Author

Untersmayr, Eva, Diesner, Susanne C., Oostingh, Gertie Janneke, Selzle, Kathrin, Pfaller, Tobias, Schultz, Cornelia, Zhang, Yingyi, Krishnamurthy, Durga, Starkl, Philipp, Knittelfelder, Regina, Förster-Waldl, Elisabeth, Pollak, Arnold, Scheiner, Otto, Pöschl, Ulrich, Jensen-Jarolim, Erika, and Duschl, Albert

Subjects
PROTEIN nitrogen, ALLERGENS, ALBUMINS, FOOD allergy, TYROSINE, METHODOLOGY, INFLAMMATION, IMMUNOGLOBULINS, LABORATORY mice
Abstract

Background: Nitration of proteins on tyrosine residues, which can occur due to polluted air under "summer smog" conditions, has been shown to increase the allergic potential of allergens. Since nitration of tyrosine residues is also observed during inflammatory responses, this modification could directly influence protein immunogenicity and might therefore contribute to food allergy induction. In the current study we have analyzed the impact of protein nitration on sensitization via the oral route. Methodology/Principal Findings: BALB/c mice were immunized intragastrically by feeding untreated ovalbumin (OVA), sham-nitrated ovalbumin (snOVA) or nitrated ovalbumin (nOVA) with or without concomitant acid-suppression. To analyze the impact of the sensitization route, the allergens were also injected intraperitoneally. Animals being fed OVA or snOVA under acid-suppressive medication developed significantly elevated levels of IgE, and increased titers of specific IgG1 and IgG2a antibodies. Interestingly, oral immunizations of nOVA under anti-acid treatment did not result in IgG and IgE formation. In contrast, intraperitoneal immunization induced high levels of OVA specific IgE, which were significantly increased in the group that received nOVA by injection. Furthermore, nOVA triggered significantly enhanced mediator release from RBL cells passively sensitized with sera from allergic mice. Gastric digestion experiments demonstrated protein nitration to interfere with protein stability as nOVA was easily degraded, whereas OVA and snOVA remained stable up to 120 min. Additionally, HPLC-chip-MS/MS analysis showed that one tyrosine residue (Y107) being very efficiently nitrated is part of an ovalbumin epitope recognized exclusively after oral sensitization. Conclusions/Significance: These data indicated that despite the enhanced triggering capacity in existing allergy, nitration of OVA may be associated with a reduced de novo sensitizing capability via the oral route due to enhanced protein digestibility and/or changes in antibody epitopes. [ABSTRACT FROM AUTHOR]

Published
2010
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49. The High Affinity IgE Receptor FcϵRI Is Expressed by Human Intestinal Epithelial Cells.

Author

Untersmayr, Eva, Bises, Giovanna, Starkl, Philipp, Bevins, Charles L., Scheiner, Otto, Boltz-Nitulescu, George, Wrba, Fritz, and Jensen-Jarolim, Erika

Subjects
IMMUNOGLOBULIN E, CANCER patients, EPITHELIAL cells, EXFOLIATIVE cytology, COLON cancer, PATHOLOGICAL physiology, INFLAMMATION, IMMUNOHISTOCHEMISTRY, CANCER cells
Abstract

Background: IgE antibodies play a paramount role in the pathogenesis of various intestinal disorders. To gain insights in IgE-mediated pathophysiology of the gut, we investigated the expression of the high affinity IgE receptor FcϵRI in human intestinal epithelium. Methodology/Principal Findings: FcϵRI α-chain, as detected by immunohistochemistry, was positive in epithelial cells for eight of eleven (8/11) specimens from colon cancer patients and 5/11 patients with inflammation of the enteric mucosa. The FceRIa positive epithelial cells co-expressed FcϵRIγ, whereas with one exception, none of the samples was positive for the β-chain in the epithelial layer. The functionality of FcϵRI was confirmed in situ by human IgE binding. In experiments with human intestinal tumor cell lines, subconfluent Caco-2/TC7 and HCT-8 cells were found to express the α- and γ-chains of FcϵRI and to bind IgE, whereas confluent cells were negative for c-chains. Conclusions/Significance: Our data provide the first evidence that the components of a functional FceRI are in vitro expressed by the human intestinal epithelial cells depending on differentiation and, more importantly, in situ in epithelia of patients with colon cancer or gastrointestinal inflammations. Thus, a contribution of FceRI either to immunosurveillance or pathophysiology of the intestinal epithelium is suggested. [ABSTRACT FROM AUTHOR]

Published
2010
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50. Anti-ulcer treatment during pregnancy induces food allergy in mouse mothers and a Th2-bias in their offspring.

Author

Schöll, Isabella, Ackermann, Ute, Özdemir, Cevdet, Blümer, Nicole, Dicke, Tanja, Sel, Serdar, Sel, Sarper, Wegmann, Michael, Szalai, Krisztina, Knittelfelder, Regina, Untersmayr, Eva, Scheiner, Otto, Garn, Holger, Jensen-Jarolim, Erika, and Renz, Harald

Subjects
ACIDS, PREGNANT women, ALLERGENS, IMMUNE response, LACTATION
Abstract

The treatment of dyspeptic disorders with anti-acids leads to an increased risk of sensitization against food allergens. As these drugs are taken by 30-50% of pregnant women due to reflux and heart-burn, we aimed here to investigate the impact of maternal therapy with anti-acids on the immune response in the offspring in a murine model. Codfish extract as model allergen was fed with or without sucralfate, an anti-acid drug, to pregnant BALB/c mice during pregnancy and lactation. These mothers developed a codfish-specific allergic response shown as high IgG1 and IgE antibody levels and positive skin tests. In the next step we analyzed whether this maternal sensitization impacts a subsequent sensitization in the offspring. Indeed, in stimulated splenocytes of these offspring we found a relative Th2-dominance, because the Th1- and T-regulatory cytokines were significantly suppressed. Our data provide evidence that the anti-acid drug sucralfate supports sensitization against food in pregnant mice and favors a Th2-milieu in their offspring. From these results we propose that anti-acid treatment during pregnancy could be responsible for the increasing number of sensitizations against food allergens in young infants. [ABSTRACT FROM AUTHOR]

Published
2007
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