Biomedical subjects

Otto Scheiner

Publications and source records attributed to Otto Scheiner.

At least 19 recordsLinked to original sources

PubMed2007

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

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 heartburn, 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.

Animals↗

PubMed2007

Incomplete digestion of codfish represents a risk factor for anaphylaxis in patients with allergy.

BACKGROUND: Fish represents one of the most important allergenic foods causing severe allergic reactions. Nevertheless, it has been shown that gastric digestion significantly reduces its allergenic capacity. OBJECTIVE: In this study, we assessed the absorption kinetics of fish proteins and investigated the clinical reactivity of patients with fish allergy to codfish digested at physiological or elevated gastric pH. METHODS: Healthy individuals were openly challenged with codfish and blood samples were evaluated by histamine release for absorbed fish allergens. Patients with allergy were recruited on the basis of previously diagnosed codfish allergy. Fish extracts were digested with gastric enzymes at pH 2.0 and 3.0 and used for histamine release, skin prick tests, and titrated double-blind placebo-controlled food challenges. RESULTS: Ingestion experiments in subjects without allergy revealed absorption of biologically active fish allergens only 10 minutes after ingestion with maximal serum levels after 1 to 2 hours. Incubation of fish proteins with digestive enzymes at pH 2.0 resulted in a fragmentation of the proteins leading to a reduced biological activity evidenced by a significantly smaller wheal reaction and reduced histamine release. Fish digested at pH 3.0 revealed comparable reactivity patterns as undigested extracts. Moreover, these test materials triggered reactions at 10-fold to 30-fold lower cumulated challenge doses in patients with allergy. CONCLUSION: Our data indicate the paramount importance of gastric digestion for fish allergens because the quantitatively significant absorption and elicitation of symptoms seemed to take place in the intestine. CLINICAL IMPLICATIONS: Hindered digestion puts patients with fish allergy at risk to develop severe allergic reactions at minute amounts of allergens.

Adult↗

PubMed2007

Delayed tumor onset and reduced tumor growth progression after immunization with a Her-2/neu multi-peptide vaccine and IL-12 in c-neu transgenic mice.

Passive immunotherapy with monoclonal antibodies is a routinely performed but cost intensive treatment against certain cancers. Induction of humoral anti-tumor responses by active peptide immunization has therefore become a favorable treatment concept. We have recently identified three peptides representing B-cell epitopes of the extracellular domain of Her-2/neu each of them inducing Her-2/neu specific immune responses with anti-tumor activity in vitro. The present study was performed to evaluate the in vivo protective capacity of a combined vaccination with these three peptides in FVB/N transgenic mice spontaneously developing c-neu overexpressing breast cancers. The three Her-2/neu peptides coupled to tetanus toxoid were administered with or without addition of recombinant IL-12. At the time all untreated mice had developed tumors about 40% of peptide-immunized mice and nearly 60% of mice immunized with the peptide vaccine co-applied with IL-12 remained tumor free. Moreover, co-administration of IL-12 had a significant impact on the retardation of tumor progression. The enhanced anti-tumor efficacy of the vaccine by IL-12 was associated with a Th1 biased immune response as demonstrated by an increased IFN-gamma production in vitro and elevated Her-2-specific IgG levels. Our findings clearly demonstrate that this multi-peptide vaccine is effective in tumor prevention and support its use against minimal disease, drug-resistant tumors or even for prophylaxis against cancers overexpressing Her-2/neu.

Adjuvants, Immunologic↗

PubMed2006

Internal images: human anti-idiotypic Fab antibodies mimic the IgE epitopes of grass pollen allergen Phl p 5a.

BACKGROUND: The role of anti-idiotypic antibodies in allergic disease is still poorly understood. According to Jerne, anti-idiotypic antibodies to IgE should represent internal images of an allergen. Our aim was to ultimately prove whether this hypothesis holds true in allergy. Here, we describe the selection of anti-idiotypic antibodies against Phl p 5a-specific IgE directly from the B-cell repertoire of a grass pollen allergic individual. METHODS: Taking Phleum pratense grass pollen allergen Phl p 5 as a model, we selected anti-idiotypic antibodies against allergen-specific IgE directly from the B-cell repertoire of an allergic individual. We screened a combinatorial phage display library of human monovalent antibody heavy and light chain fragments (Fabs) with anti-Phl p 5a-IgE to identify and characterize Fabs with anti-idiotypic specificity. RESULTS: Five different Fab clones with anti-idiotypic specificity for anti-Phl p 5a-IgE were identified. Their hypervariable regions revealed partial sequence homology with solvent accessible antigenic sites of Phl p 5a, which have been identified by our previous mimotope approach. Phagemid DNA derived from the phage clones was used to produce two soluble recombinant anti-idiotypic Fab clones in E. coli. As a proof of molecular mimicry, both Fabs induced anti-Phl p 5a-specific antibodies in immunized BALB/c mice. Molecular modeling of the heavy and light chain hypervariable loops of the anti-idiotypic Fabs illustrated structural similarity with dominant IgE epitopes of Phl p 5a. CONCLUSION: In this straightforward phage technology approach, antibodies with anti-idiotypic specificities could be isolated from a human allergic's repertoire. As predicted by the immune network hypothesis, their hypervariable domains mimic IgE epitopes like internal images and, more importantly, induce allergen-specific immune responses in the absence of the allergen.

Amino Acid Sequence↗

PubMed2006

Induction of IgG antibodies against the GD2 carbohydrate tumor antigen by vaccination with peptide mimotopes.

The disialoganglioside GD2, a carbohydrate antigen, is expressed on all tumors of neuroectodermal origin, including melanoma, neuroblastoma, sarcoma and small cell lung cancer. Due to its specific expression on tumor surfaces, GD2 is an attractive target for immunotherapies. The mouse/human chimeric anti-GD2 mAb ch14.18 is already applied in melanoma and neuroblastoma trials as a passive immunotherapy. To establish an active immunotherapy alternative, we aimed to replace the poorly immunogenic ganglioside with immunogenic peptides. Previously, we used the ch14.18 antibody to select GD2 peptide mimics from a phage display library. In the present study, two mimics of the ch14.18 epitope were coupled to keyhole limpet hemocyanin and used for immunizing BALB/c mice. Induction of a specific humoral immune response towards the original antigen GD2, both purified and expressed on neuroblastoma and melanoma cells, could be demonstrated in ELISA, Western blot, and immunofluorohistochemistry. As the elicited antibodies were of the IgG isotype, the mimotope conjugates were capable of recruiting T cell help and inducing memory phenomena. In conclusion, we show that an epitope of the carbohydrate antigen GD2 can successfully be translated into immunogenic peptide mimotopes. Our immunization experiments indicate that GD2 mimotopes are suitable for active immunotherapy of GD2-expressing tumors.

Animals↗

PubMed2005

Vaccination with cetuximab mimotopes and biological properties of induced anti-epidermal growth factor receptor antibodies.

BACKGROUND: The monoclonal antibody cetuximab (IMC-225, Erbitux) inhibits epidermal growth factor receptor (EGFR) signaling and has been approved for metastatic colon cancer therapy. However, to achieve effective titers, passive antibody therapies must be repeatedly administered over long periods. To overcome this limitation, we aimed to generate a vaccine inducing continuously available "cetuximab-like" antibodies in vivo using the mimotope approach. METHODS: We used the phage display technique to identify four peptides structurally mimicking the cetuximab epitope. We coupled two of these peptides to an immunogenic carrier protein, and we vaccinated four groups (n = 8) of BALB/c mice intraperitoneally with 10 microg of the mimotope conjugates, a control peptide conjugate, or the carrier protein alone. We assessed antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity mediated by the induced antibodies against EGFR-overexpressing human A431 carcinoma cells. We then tested receptor internalization capacity of the induced antibodies with fluorescently labeled EGFR, and we assayed their growth inhibitory potential toward A431 cells with a [3H]thymidine proliferation assay. RESULTS: Mimotope-induced antibodies recognized EGFR, and both types of antibody-mediated cytotoxic effects were elicited by these antibodies. In both cellular cytotoxicity assays, the mimotope-induced antibodies exhibited specific lysis of more than 50%. The induced antibodies caused internalization of the receptor from the cell surface into endocytic vesicles and inhibited growth of EGFR-expressing cells to a similar extent as cetuximab [67% (95% confidence interval {CI} = 55% to 79%) and 69% (95% CI = 55% to 84%), respectively]. CONCLUSIONS: Epitope-specific immunization is feasible for active anti-EGFR immunotherapy. The in vitro biologic features of mimotope-induced antibodies are similar to those of the monoclonal antibody cetuximab.

Animals↗

PubMed2005

Dimerization of the major birch pollen allergen Bet v 1 is important for its in vivo IgE-cross-linking potential in mice.

In type I allergy, the cross-linking of membrane IgE on B lymphocytes and of cytophilic IgE on effector cells by their respective allergens are key events. For cross-linking two IgE molecules, allergens need at least two epitopes. On large molecules, these could be different epitopes in a multivalent, or identical epitopes in a symmetrical, fashion. However, the availability of epitopes may be limited on small allergens such as Bet v 1, the major birch pollen allergen. The present work analyzes whether dimerization is required for the cross-linking capacity of this allergen. In immunoblots, murine monoclonal and polyclonal human Bet v 1-specific Abs detected, besides a Bet v 1 monomer of 17 kDa, a dimer of 34 kDa. In dynamic light scattering, Bet v 1 appeared as dimers and even multimers, but a single condition could be defined where it behaved exclusively monomerically. Small-angle x-ray scattering of the monomeric and dimeric samples resulted in diagrams agreeing with the calculated models. Circular dichroism measurements indicated that the structure of Bet v 1 was preserved under monomeric conditions. Skin tests in Bet v 1-allergic mice were positive with Bet v 1 dimer, but remained negative using the monomer. Furthermore, in contrast to dimeric Bet v 1, the monomer was less capable of activating murine memory B cells for IgE production in vivo. Our data indicate that the presentation of two identical epitopes by dimerized allergens is a precondition for cross-linking of IgE on mast cells and B lymphocytes.

Allergens↗

PubMed2005

Targeting antigens to murine and human M-cells with Aleuria aurantia lectin-functionalized microparticles.

Neuraminidases act as a virulence factors for several pathogens that invade the human body through Peyer's patch M-cells. Because of the structural similarity of Aleuria aurantia lectin (AAL) to neuraminidases, we hypothesized that AAL might also target human M-cells. In an in vitro human M-cell co-culture model significantly more particles were transported across the epithelium when microparticles were functionalized with AAL versus those that were not. Moreover, high concentrations of AAL induced no detectable cytotoxic effects on the related intestinal epithelial cell cultures, epithelial Caco2- and HT29-MTX-E12-cells. Upon incubation with AAL, PBMCs of allergic volunteers proliferated in response to AAL and secreted the cytokines, IL-2, IFN-gamma, IL-10 and IL-5 in a concentration-dependent manner, indicating immune-stimulatory properties of the lectin. We conclude that AAL-coated microparticles may have the potential to target entrapped antigens to human M-cells for oral vaccination.

Allergens↗

PubMed2005

Mimotopes identify conformational epitopes on parvalbumin, the major fish allergen.

Parvalbumin, the major fish allergen, is recognized by allergen-specific IgE of more than 90% of all fish-allergic patients. A detailed knowledge of allergenic structures is crucial for developing a vaccine inducing blocking antibodies specifically directed towards the IgE binding epitopes. In the present study we aimed to use the phage display technique to generate mimotopes, which mimic epitopes on parvalbumin. Parvalbumin-specific IgE was purified from sera of fish-allergic patients and used for screening of a constrained decamer phage library. After four rounds of biopanning using parvalbumin-specific IgE, five phage clones were selected which were specifically recognized by parvalbumin-specific IgE as well as IgG. DNA sequencing and peptide alignment revealed a high degree of sequence similarities between the mimotopes. Interestingly, on the surface of natural parvalbumin three regions could be defined by computational mimotope matching. In accordance, previously defined allergenic peptides of cod parvalbumin highlighted areas in close proximity or overlapping with the mimotope matching sites. From the presented data we conclude that our approach identified conformational epitopes of parvalbumin relevant for IgE and IgG binding. We suggest that these mimotopes are suitable candidates for an epitope-specific immunotherapy of fish-allergic patients.

Allergens↗

PubMed2005

Mucosal targeting of allergen-loaded microspheres by Aleuria aurantia lectin.

Murine intestinal M-cells express alpha-L-fucose residues. We constructed alpha-L-fucose-targeting particles for oral immunotherapy of IgE-mediated allergy. Poly(D,L-lactic-co-glycolic acid)-microspheres were loaded with birch pollen allergens, and functionalised with the alpha-L-fucose specific Aleuria aurantia lectin (AAL). The AAL-microspheres had a size of 1-3 microm, protected the entrapped allergens from gastric degradation and released 46.6+/-1.3% allergen over 21 days in vitro. Oral gavages of AAL-particles to naive BALB/c mice induced birch pollen-specific IgG2a, but not IgG1 antibodies. We conclude that targeting allergens to alpha-L-fucose-receptor bearing cells using AAL-microspheres induces specific Th1-antibody responses possibly counteracting Th2-dominated allergy, and therefore provides a potentially useful formulation for oral immunotherapy.

Allergens↗

PubMed2005

Suppression of human melanoma tumor growth in SCID mice by a human high molecular weight-melanoma associated antigen (HMW-MAA) specific monoclonal antibody.

The lack of efficacy of available therapies for the treatment of malignant melanoma has emphasized the need to develop novel therapeutic strategies to prevent melanoma growth. We have tested whether the anti-HMW-MAA mAb 225.28S is able to inhibit human melanoma tumor growth in SCID mice because in vitro data suggested that this antigen plays a role in spreading, migration and invasion of melanoma cells. Tumors were established by subcutaneous injection of the human melanoma cell line 518A2 into SCID mice. When tumors reached a size of 5 mm, the mAb 225.28S was administered intravenously 4 times in 3 day intervals at 100 microg/injection. Within 14 days after the first administration of the mAb 225.28S, tumor growth was reduced by 52% as compared to control mice. Three hundred and seven genes of >20,000 genes contained on the GeneChip were changed in their expression level at least 2-fold after administration of the mAb 225.28S. The encoded proteins were mostly components or modifiers of the extracellular matrix, tumor suppressors, and melanogenesis associated proteins. Surprisingly, the administration of the control mAb that did not lead to a significant tumor growth inhibition in vivo resulted in the modulation of two-thirds of these genes. This is the first report of suppression of human melanoma tumor growth in SCID mice by the mAb 225.28S. Our results suggest that anti-HMW-MAA mAbs may represent useful reagents to apply passive immunotherapy to patients with malignant melanoma.

Animals↗

PubMed2005

Entamoeba histolytica: analysis of the trophozoite proteome by two-dimensional polyacrylamide gel electrophoresis.

The Entamoeba histolytica genome project carried out at TIGR and the Sanger Institute has produced a near-complete set of deduced open reading frame sequences. These data provide strong support for the identification of signals from proteomic analyses such as two-dimensional electrophoresis by protein sequencing and/or mass spectrometric methods. To carry out an initial investigation of the E. histolytica proteome, appropriate sample preparation and silver staining protocols were adapted. After preparation of protein extracts from E. histolytica HM-1:IMSS trophozoites, solubilized proteins were separated in the first dimension in IPG (immobilized pH gradient) strips depending on their pI and subsequently in the second dimension according to their molecular weight by SDS-polyacrylamide gel electrophoresis. Of the more than 1500 protein spots visualized, several landmark spots were isolated from the gels and identified by either tryptic cleavage and subsequent MALDI-TOF mass spectrometry or by protein sequencing.

Animals↗

PubMed2005

Anti-ulcer drugs promote IgE formation toward dietary antigens in adult patients.

Recently, we have demonstrated that anti-ulcer drugs, such as H2-receptor blockers and proton pump inhibitors, promote the development of immediate type food allergy toward digestion-labile proteins in mice. The aim of this study was to examine the allergological relevance of these findings in humans. In an observational cohort study, we screened 152 adult patients from a gastroenterological outpatient clinic with negative case histories for atopy or allergy, who were medicated with H2-receptor blockers or proton pump inhibitors for 3 months. IgE reactivities to food allergens before and after 3 months of anti-acid treatment were compared serologically. Ten percent of the patients showed a boost of preexisting IgE antibodies and 15% de novo IgE formation toward numerous digestion-labile dietary compounds, like milk, potato, celery, carrots, apple, orange, wheat, and rye flour. Thus, the relative risk to develop food-specific IgE after anti-acid therapy was 10.5 (95% confidence interval: 1.44-76.48). The long-term effect was evaluated 5 months after therapy. Food-specific IgE could still be measured in 6% of the patients, as well as significantly elevated serum concentrations of ST2, a Th2-specific marker. An unspecific boost during the pollen season could be excluded, as 50 untreated control patients revealed no changes in their IgE pattern. In line with our previous animal experiments, our data strongly suggest that anti-ulcer treatment primes the development of IgE toward dietary compounds in long-term acid-suppressed patients.

Adult↗

PubMed2005

Vaccination with a human high molecular weight melanoma-associated antigen mimotope induces a humoral response inhibiting melanoma cell growth in vitro.

Peptide mimics of a conformational epitope that is recognized by a mAb with antitumor activity are promising candidates for formulations of anticancer vaccines. These mimotope vaccines are able to induce a polyclonal Ab response focused to the determinant of the mAb. Such attempts at cancer immunotherapy are of special interest for malignant melanoma that is highly resistant to chemotherapy and radiotherapy. In this study, we describe for the first time the design and immunogenicity of a vaccine containing a mimotope of the human high m.w. melanoma-associated Ag (HMW-MAA) and the biological potential of the induced Abs. Mimotopes were selected from a pVIII-9mer phage display peptide library with the anti-HMW-MAA mAb 225.28S. The mimotope vaccine was then generated by coupling the most suitable candidate mimotope to tetanus toxoid as an immunogenic carrier. Immunization of rabbits with this vaccine induced a specific humoral immune response directed toward the epitope recognized by the mAb 225.28S on the native HMW-MAA. The induced Abs inhibited the in vitro growth of the melanoma cell line 518A2 up to 62%. In addition, the Abs mediated 26% lysis of 518A2 cells in Ab-dependent cellular cytotoxicity. Our results indicate a possible application of this mimotope vaccine as a novel immunotherapeutic agent for the treatment of malignant melanoma.

Amino Acid Sequence↗

PubMed2005

Matching of trastuzumab (Herceptin) epitope mimics onto the surface of Her-2/neu--a new method of epitope definition.

As seen with the proto-oncogene Her-2/neu, antibodies targeting different parts of a receptor can have opposing effects. Depending on epitope specificity, in this case, tumor growth can be inhibited--but also enhanced. Therefore, the definition of molecular binding sites is of increasing importance in modern medicine. We here introduce a novel approach for binding site localization, utilizing information obtained by the phage display technique. This is a high throughput screening method for identification of peptide mimics, so called mimotopes, of any binding structure of interest. All target molecules whose structure is available in the RCSB Protein Data Bank can be scanned for mimotope matches on their surface. In this study, we present the matching results of five mimotopes defined for the epitope recognized by trastuzumab (Herceptin), a humanized monoclonal antibody inhibiting tumor growth, on Her-2/neu. The localization thus obtained corresponds to the known trastuzumab epitope. We therefore suggest the algorithm as a novel way of binding site definition, circumventing co-crystallization experiments.

Algorithms↗

PubMed2005

Intranasal tolerance induction with polypeptides derived from 3 noncross-reactive major aeroallergens prevents allergic polysensitization in mice.

BACKGROUND: Specific immunotherapy is less effective in patients with multiple allergic sensitizations compared with monosensitized patients. OBJECTIVE: We therefore established a mouse model of polysensitization to the major birch and timothy grass pollen allergens to test whether allergic polysensitization can be prevented by multiple allergen application via the mucosal route. METHODS: Female BALB/c mice were immunized intraperitoneally with recombinant (r) Bet v 1, rPhl p 1, and rPhl p 5. For intranasal tolerance induction, a mixture of the complete allergens was compared with allergen-derived immunodominant peptides applied either as a mixture or as a synthetic hybrid peptide composed of the T-cell epitopes of the 3 allergens. RESULTS: Intranasal application of the mixture of the complete allergen molecules did not prevent polysensitization to the same allergens. In contrast, pretreatment with a mixture of the immunodominant peptides or the hybrid peptide led to significantly reduced allergen-specific IgE responses in sera, IL-4 production in vitro, and suppressed airway inflammation. TGF-beta mRNA levels did not change, and IL-10 production was significantly suppressed after the pretreatment. The fact that the reduction of IL-10 was not abrogated after IL-10 receptor neutralization and that tolerance was not transferable with splenocytes indicates that the suppression of T(H)2 responses in polysensitized mice might not be mediated by immunosuppressive cytokines. CONCLUSION: Our study demonstrates that it is possible to suppress allergic immune responses simultaneously to several clinical important allergens. Thus, mucosal coapplication of selected peptides/hybrid peptides could be the basis of a mucosal polyvalent vaccine to prevent multiple sensitivities in atopic patients.

Allergens↗

PubMed2005

Isolation and structural analysis of peptide mimotopes for the disialoganglioside GD2, a neuroblastoma tumor antigen.

The disialoganglioside GalAcbeta1-4(NeuAcalpha2-8NeuAcalpha2-3)Galbeta1-4Glcbeta1-1Cer (GD2) is expressed on various tumors, including neuroblastoma, and was defined as a relevant tumor antigen. The monoclonal anti-GD2 antibody 14.18 is widely used for diagnostic purposes in neuroblastoma, and in its mouse/human chimeric form (ch14.18) now enters passive immunotherapeutic regimens in phase II clinical trials. This study aimed to generate structural mimics of the 14.18 epitope of GD2. Therefore, we used the ch14.18 antibody for selecting immunoreactive GD2 peptide mimotopes from a decamer phage display library. In all, 13 GD2 peptide mimics could be determined by biopanning and their specificity was demonstrated by exclusive recognition by the ch14.18 antibody. Furthermore, their nature of being GD2 mimics and their degree of mimicry was confirmed by competition with the natural antigen. When performing a comparative visualization of the GD2 epitope and selected mimotopes using a three-dimensional computer modeling system (BALLView), we demonstrated fitting of the GD2 molecule and the mimotopes in the antigen-binding pouch of a GD2 specific antibody. Moreover, the computer modeling argued for optimal affinity of the GD2 mimotopes. We thus provide evidence that the generation of GD2 peptide mimotopes is successful when using the neuroblastoma antibody ch14.18 for selection, and that this approach might offer a tool to develop a vaccination strategy against this malignant pediatric tumor.

Amino Acid Sequence↗

PubMed2005

Antiulcer drugs promote oral sensitization and hypersensitivity to hazelnut allergens in BALB/c mice and humans.

BACKGROUND: Hazelnut allergy can be a consequence of sensitization to cross-reactive pollen, especially from the Fagales family. However, severe allergic reactions after ingestion of hazelnuts without associated pollen allergy have been reported. In these cases, oral sensitization by hazelnut ingestion is plausible. OBJECTIVE: We have reported that antiulcer drugs promote oral sensitization to digestion-labile food allergens. Because hazelnut proteins were sensitive to gastric digestion in our in vitro assay, we aimed to analyze the effect of antiulcer treatment on oral sensitization to hazelnut proteins. DESIGN: BALB/c mice were fed hazelnut extract with or without antiulcer drugs. In parallel, gastroenterologic patients (n = 153) were screened during antiulcer treatment for specific immunoglobulin (Ig) E to hazelnut and inhalative allergens in vitro and in vivo. RESULTS: Mice fed hazelnut extract in combination with antiulcer drugs formed anaphylactogenic IgG1 toward hazelnut and developed type I skin reactivity to hazelnut extract. In the human study population, 5 of 153 (3.3%) patients developed hazelnut-specific IgE, 4 of 5 developed specific skin reactivity, 3 of 5 had a positive result to oral provocation, and 2 of 5 manifested a food allergy to hazelnut after a 3-mo course of antiulcer treatment. Immunoblot testing with recombinant allergens showed that hazelnut, but not Fagales pollen, was the genuine elicitor in mice and humans. CONCLUSION: Our experimental and epidemiologic data suggest that the intake of antiulcer drugs may lead to the induction of immediate-type food hypersensitivity toward hazelnut.

Adult↗