Cutaneous reaction to ifosfamide plus mesna treated with desensitization challenge: a case report.

BACKGROUND: Ifosfamide is an alkylating agent used in the treatment of a wide range of tumours. Because of known side effects it is usually administered in combination with mesna, a thiol agent with uroprotective activity, to reduce them and increase the therapeutic dose. The most frequently administered regimens for ifosfamide are fractionated doses for 3 to 5 days, high-dose intravenous bolus, and continuous infusion over 24 to 72 h. Hypersensitivity reactions to ifosfamide plus mesna are not frequently described in the literature. Moreover, no reports exist concerning desensitization for this chemotherapy combination. CASE PRESENTATION: A 47-year-old man with stage IV renal sarcoma was treated with the combination of ifosfamide and mesna every 3 weeks in a 4-consecutive-day infusion protocol. During the second cycle of chemotherapy, he presented acute cutaneous symptoms. A 12-step desensitization protocol was proposed in view of the lack of knowledge of the possible hypersensitivity reactions to this combination of chemotherapy agents, and the multiple difficulties found during the study of the case. CONCLUSIONS: The 12-step desensitization protocol was well tolerated. Therefore, it is an appropriate and safe option in the case of suspected allergy to ifosfamide plus mesna.

Geographical differences in food allergy.

BACKGROUND: Food allergy represents a health problem worldwide and leads to life-threatening reactions and even impairs quality of life. Epidemiological data during the past decades is very heterogeneous because of the use of different diagnostic procedures, and most studies have only been performed in specific geographical areas. OBJECTIVES: The aim of this article is to review the available data on the geographical distribution of food allergies at the food source and molecular level and to link food allergy patterns to the aeroallergen influence in each area. METHODS: Systematic reviews, meta-analysis, studies performed within the EuroPrevall Project and EAACI position papers regarding food allergy were analysed. CONCLUSIONS: The prevalence of food allergy sensitization differs between geographical areas, probably as a consequence of differences among populations, their habits and the influence of the cross-reactivity of aeroallergens and other sources of allergens. Geographical differences in food allergy are clearly evident at the allergenic molecular level, which seems to be directly influenced by the aeroallergens of each region and associated with specific clinical patterns.

Immunotherapy (oral and sublingual) for food allergy to fruits.

BACKGROUND: Food allergy is an abnormal immunological response following exposure (usually ingestion) to a food. Elimination of the allergen is the principle treatment for food allergy, including allergy to fruit. Accidental ingestion of allergenic foods can result in severe anaphylactic reactions. Allergen-specific immunotherapy (SIT) is a specific treatment, when the avoidance of allergenic foods is problematic. Recently, studies have been conducted on different types of immunotherapy for the treatment of food allergy, including oral (OIT) and sublingual immunotherapy (SLIT). OBJECTIVES: To determine the efficacy and safety of oral and sublingual immunotherapy in children and adults with food allergy to fruits, when compared with placebo or an elimination strategy. SEARCH METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and AMED were searched for published results along with trial registries and the Journal of Negative Results in BioMedicine for grey literature. The date of the most recent search was July 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing OIT or SLIT with placebo or an elimination diet were included. Participants were children or adults diagnosed with food allergy who presented immediate fruit reactions. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by the Cochrane Collaboration. We assessed treatment effect through risk ratios (RRs) for dichotomous outcomes. MAIN RESULTS: We identified two RCTs (N=89) eligible for inclusion. These RCTs addressed oral or sublingual immunotherapy, both in adults, with an allergy to apple or peach respectively. Both studies enrolled a small number of participants and used different methods to provide these differing types of immunotherapy. Both studies were judged to be at high risk of bias in at least one domain. Overall, the quality of evidence was judged to be very low due to the small number of studies and participants and possible bias. The studies were clinically heterogeneous and hence we did not pool the results. A study comparing SLIT with placebo for allergy to peach did not detect a significant difference between the number of patients desensitised at six months following a double-blind placebo-controlled food challenge (RR 1.16, 95% confidence interval (CI) 0.49 to 2.74). The second study, comparing OIT versus no treatment for apple allergy, found an effect on desensitisation in favour of the intervention using an oral provocation test at eight months, but results were imprecise (RR 17.50, 95% CI 1.13 to 270.19). Neither study reported data on evidence of immunologic tolerance. In both studies, the incidence of mild and moderate adverse events was higher in the intervention groups than in the controls. In the study comparing SLIT with placebo, patients in the intervention group experienced significantly more local adverse reactions than participants in the control group (RR 3.21, 95% CI 1.51 to 6.82), though there was not a significant difference in the number of participants experiencing systemic adverse reactions (RR 0.81, 95% CI 0.22 to 3.02). In the study of OIT, two of the 25 participants in the intervention group reported relevant side effects, whereas no participants in the control group reported relevant side effects. AUTHORS' CONCLUSIONS: There is insufficient evidence for using OIT or SLIT to treat allergy to fruit, specifically related to peach and apple. Mild or moderate adverse reactions were reported more frequently in people receiving OIT or SLIT. However, these reactions could be treated successfully with medications.

Pomegranate ( Punica granatum L.) expresses several nsLTP isoforms characterized by different immunoglobulin E-binding properties.

BACKGROUND: Pomegranate allergy is associated with sensitization to non-specific lipid transfer proteins (nsLTPs). Our aim was to identify and characterize the non-specific nsLTPs expressed in pomegranate at the molecular level and to study their allergenic properties in terms of immunoglobulin E (IgE)-binding and cross-reactivity with peach nsLTP (Pru p 3). METHODS: A non-equilibrium two-dimensional (2-D) electrophoretic approach based on acid-urea PAGE and sodium dodecyl sulfate PAGE was set up to separate pomegranate nsLTPs. Their immunoreactivity was tested by immunoblotting carried out with anti-Pru p 3 polyclonal antibodies and sera from pomegranate-allergic patients. For final identification, pomegranate nsLTPs were purified by chromatography and subjected to trypsin digestion and mass spectrometry (MS) analysis. For this purpose, the sequences obtained by cDNA cloning of three pomegranate nsLTPs were integrated in the database that was subsequently searched for MS data interpretation. RESULTS: Four nsLTPs were identified by 2-D immunoblotting. The detected proteins showed different IgE-binding capacity and partial cross-reactivity with Pru p 3. cDNA cloning and MS analyses led to the identification of three nsLTP isoforms with 66-68% amino acid sequence identity named Pun g 1.0101, Pun g 1.0201 and Pun g 1.0301. CONCLUSIONS: By 2-D electrophoresis, we could separate different nsLTP isoforms possessing different IgE-binding properties, which might reflect peculiar allergenic potencies. The contribution of Pru p 3 to prime sensitization is not central as in other plant nsLTPs.

Large bowel obstruction secondary to a cecal bascule with internal herniation through the foramen of Winslow: A case report.

INTRODUCTION: Internal hernias are a rare phenomenon, and even rarer is a herniation through the foramen of Winslow. The clinical presentation of patients with an internal hernia is often vague and difficult to diagnose clinically. If internal hernias go undiagnosed and untreated, patients can develop bowel compromise leading to a high morbidity and potential mortality. Radiologic imaging is helpful in bringing the diagnosis to the forefront of the clinicians mind, but the diagnosis is often made intra-operatively. PRESENTATION OF CASE: An eighty-one year old female presenting with a few months of vague abdominal symptoms who was found to have a cecal bascule internally herniating through the foramen of Winslow was treated successfully with surgical intervention. DISCUSSION: Internal hernias occur when there is a protrusion of a viscera through the peritoneum or mesentery and confined within the abdominal cavity. Internal hernias are classified according to location and vary from paraduodenal, transmesenteric, and pelvic to name a few. Hernias through the foramen of Winslow are a rare subset, and were the internal hernia found in our patient intra-operatively. Our patient's clinical presentation was vague with generic abdominal complaints and radiologic imaging was inconclusive for a definitive diagnosis. However, prompt surgical intervention resulted in a good outcome for our patient. CONCLUSION: Internal hernias, to be diagnosed and treated promptly, require a high index of suspicion from a clinician based on clinical presentation and radiologic imaging. These patients belong in the operating room, and interventions are directed based on the anatomical findings intra-operatively.

Beta-lactam allergy in patients: an antibiotic stewardship challenge.

BACKGROUND: Patients are commonly reported as being allergic to beta-lactam (BL) antibiotics. However, many patients with this reported allergy are able to receive BL treatments because they do not have true allergies. In many cases these are simply intolerances due to side effects reported as an allergy. Delabelling these patients leads to better clinical outcomes, optimal antibiotic usage, decreased bacterial resistance and reduced healthcare costs. Therefore, the aims of this study were to identify incorrectly labelled BL allergies in hospitalised patients and to assess antibiotic use in delabelled patients in order to establish a quality indicator to optimise antimicrobial treatments. METHODS: A prospective study was conducted in which hospitalised patients treated with antimicrobial drugs and labelled as 'BL-allergic' were identified by clinical pharmacists. An allergist assessed whether patients were suitable candidates for a skin test or oral challenge. The Allergy Service removed 'BL-allergic' labels if negative results were obtained. Delabelled patients were followed up by clinical pharmacists to study the use of BL antibiotics as a result of the delabelling programme. RESULTS: A total of 176 suspected allergic patients were identified and 91 (51.7%) were tested either by a skin test or oral challenge based on the patient indicators. Seven (16.4%) patients tested were allergic to BL antibiotics, 76 (83.5%) were totally delabelled and eight (0.1%) were partially delabelled. Thirty-two (38.1%) delabelled patients required antibiotic treatment in another inpatient or outpatient setting, of whom 27 (84.3%) patients with a new infectious episode received BL treatments while five (15.7%) continued to receive antimicrobial treatments without BL. CONCLUSION: After the implementation of a protocol to detect incorrect BL allergy labels, 83.5% of the patients in this cohort were completely delabelled. This shows that there is a clear opportunity to optimise the use of antibiotics by delabelling 'BL-allergic' patients.

Same-Day Desensitization in Patients Who Experience Their First Reaction to a Platin Agent at the Oncology Day Unit: A Pilot Study to Safely Include This Technique Within the Multidisciplinary Pathways for the Diagnosis & Management of Hypersensitivity to Platin Agents.

One of the main objectives when assessing patients who react to antineoplastics must be to ensure that they receive the required treatments without delay. From January to July 2021, at the Allergy Department at the Provincial University Consortium Hospital a pilot study was performed in which those patients suspected of having suffered a type I hypersensitivity reaction (grade 1 or 2) following Brown's anaphylaxis severity grading to a platin agent at the Provincial University Consortium oncology day unit, and once the reaction was properly treated and completely resolved, were subjected to a new procedure named as Same-Day Desensitization, which consists in the reintroduction and administration of full chemotherapy dose by allergists on the same day of the reaction by following the 1 bag/10 step protocol, looking forwards to systematize same-day reexposure using Same-Day Desensitization, doing it in the safest way possible. In total, 9 oncological patients suspected of having suffered a type I hypersensitivity reaction (grade 1 or 2) to a platin agent received total dose administration the same day of the initial reaction by following Same-Day Desensitization 1 bag/10 step protocol, without presenting further reactions. The manuscript describes a new approach in the use of Rapid Drug Desensitizations in reactive oncologic patients in treatment with platin agents, presenting the first 9 cases of oncologic patients who have been submitted to this procedure.

Yeast profilin complements profilin deficiency in transgenic tomato fruits and allows development of hypoallergenic tomato fruits.

Gene silencing of Lyc e 1 leads to reduced allergenicity of tomato fruits but impaired growth of transgenic tomato plants. The aim of the study was to restore growth of Lyc e 1-deficient tomato plants while retaining reduced allergenicity by simultaneous complementation of profilin deficiency by expression of nonallergenic yeast profilin. Transgenic plants were generated and tested by RT-PCR and immunoblotting; allergenicity of yeast profilin and transgenic fruits was investigated by IgE binding, basophil activation, and skin-prick tests. Lyc e 1 content of transgenic tomato fruits was <5% of that of wild-type plants, causing significantly reduced IgE antibody binding. Simultaneous coexpression of yeast profilin restored growth and biomass production almost to wild-type levels. Yeast profilin, sharing 32.6% amino acid sequence identity with Lyc e 1, displayed low IgE-binding capacity and allergenic potency. Among 16 tomato-allergic patients preselected for sensitization to Lyc e 1, none showed significant reactivity to yeast profilin. Yeast profilin did not induce mediator release, and coexpression of yeast profilin did not enhance the allergenicity of Lyc e 1-reduced fruits. Simultanous coexpression of yeast profilin allows silencing of tomato profilin and generation of viable plants with Lyc e 1-deficient tomato fruits. Therefore, a novel approach to allergen avoidance, genetically modified foods with reduced allergen accumulation, can be generated even if the allergen fulfills an essential cellular function in the plant. In summary, our findings of efficiently complementing profilin-deficient tomato plants by coexpression of low allergenic yeast profilin demonstrate the feasibility of creating low-allergenic food even if the allergen fulfills essential cellular functions.

Pichia pastoris is superior to E. coli for the production of recombinant allergenic non-specific lipid-transfer proteins.

Non-specific lipid-transfer proteins (nsLTP) from food and pollen are clinically important allergens, especially in patients recruited from the Mediterranean area. For the use of recombinant nsLTPs in allergy diagnosis and preclinical allergy studies the preparation of nsLTPs in a properly folded and biologically active form is required. Using hazelnut nsLTP (Cor a 8) as a model allergen, heterologous over-expression in Escherichia coli and Pichia pastoris was compared. Recombinant Cor a 8 derived from E. coli and P. pastoris was purified by IMAC and SEC or ammonium sulphate precipitation followed by IEC and SEC, respectively. The recombinant proteins were characterized with regard to IgE-binding by immunoblotting and ELISA, structure by N-terminal sequencing, CD-spectroscopy and LS and to their biological activity using an in vitro basophil histamine release assay. Purification of hazelnut nsLTP from bacterial lysate under native conditions resulted in a low yield of Cor a 8. In addition, the preparation contained non-IgE-reactive aggregations besides the IgE-reactive monomer. In contrast, the yield of rCor a 8 produced in P. pastoris was approximately 270-fold higher and impurities with oligomers have not been detected. Purified monomeric Cor a 8 from bacteria and yeast showed similar IgE-antibody reactivity and secondary structures, and both were capable of inducing histamine release from basophils. In summary, P. pastoris is superior to E. coli as expression system for the production of large quantities of soluble, properly folded, and biologically active rCor a 8.

Tolerability and positive efficacy results after subcutaneous immunotherapy with Parietaria judaica depot extract.

AIM: To evaluate tolerability and efficacy of Parietaria judaica subcutaneous immunotherapy on patients with allergic rhinoconjunctivitis. PATIENTS & METHODS: 51 patients were assigned to build-up scheme (six increasing doses) of P. judaica depot native extract, plus three maintenance monthly administrations. RESULTS: Out of 470 administered doses, only 3.8% elicited systemic reactions (1.5% nonspecific and 2.3% grade I). Concerning the exploratory efficacy parameters: cutaneous reactivity at the final visit versus baseline was significantly decreased; specific titers of IgG and IgG4 increased significantly and patients showed a significant decrease in the rhinitis symptoms score. CONCLUSION: P. judaica subcutaneous immunotherapy (Allergovac® depot ROXALL Medicina España S.A., Zamudio, Spain) with an abbreviated up-dosing scheme showed an adequate safety and tolerability profile and induced preliminary efficacy changes.

Minilaparotomy without general anesthesia for the treatment of sigmoid volvulus in high-risk patients: A case series of 4 patients.

BACKGROUND: Sigmoid volvulus (SV) is a common cause of large bowel obstruction worldwide. Presenting symptoms can be nonspecific and varied amongst the elderly population, making medical and surgical management challenging. This population is at markedly increase risk of complications and mortality with surgery under general anesthesia. In this case series, we describe 4 cases of sigmoid volvulus in octogenarians. GOALS: To demonstrate that sigmoid colectomy under local anesthesia, with or without intravenous conscious sedation, is feasible and can be done safely and with a low rate of converting to a general anesthetic. RESULTS: Four patients, mean age 90 years, were admitted a total of 4 times for acute sigmoid volvulus. All patients had serious comorbidities and were classified as ASA III. There was no relevant past surgical history. All patients were severely physically deconditioned but alert and able to interact meaningfully with their families and caregivers. Three patients suffered recurrent volvulus following endoscopic decompression and one patient underwent immediate surgery due to abdominal tenderness. CONCLUSION: Our experience demonstrates that minilaparotomy for sigmoid volvulus is effective and safe. The techniques and can extend the applicability of definitive surgical intervention to this high-risk population of patients. In our series postoperative outcomes were excellent, however, additional studies are needed to determine if this technique results in improved 30-day and long-term mortality and morbidity in high-risk patients and to determine the utility of extending the technique to all patients with sigmoid volvulus.

Design of tomato fruits with reduced allergenicity by dsRNAi-mediated inhibition of ns-LTP (Lyc e 3) expression.

Plant genetic engineering has the potential to introduce new allergenic proteins into foods but, at the same time, it can be used to remove established allergens. Here, we report the molecular characterization of Lyc e 3, a new tomato (Lycopersicon esculentum) allergen, and the efficient down-regulation of its expression in transgenic tomato plants. Following the identification of an immunoglobulin E (IgE)-binding 9-kDa polypeptide in tomato peel, designated Lyc e 3, its partial amino acid sequence was determined by N-terminal protein sequencing. Sequence comparison revealed that Lyc e 3 encodes a nonspecific lipid transfer protein (ns-LTP). In plants, ns-LTPs are encoded by large gene families which differ in primary amino acid sequence, expression and proposed cellular function. To identify Lyc e 3 encoding complementary DNAs (cDNAs), public tomato expressed sequence tag (EST) databases were screened for ns-LTP sequences. Following this strategy, two cDNAs, LTPG1 and LTPG2, with high homology to the N-terminal sequence of Lyc e 3, were identified. Ectopic expression of LTPG1 and LTPG2 in Escherichia coli, followed by immunoblotting, verified their IgE reactivity. Subsequently, transgenic tomato plants constitutively expressing LTPG1- or LTPG2-specific double-stranded RNA interference (dsRNAi) constructs were created and tested for the suppression of Lyc e 3 accumulation. Efficient silencing of Lyc e 3 was documented by Northern and Western blotting. In both cases, Lyc e 3 accumulation was decreased to levels below the detection limit (less than 0.5% of the wild-type protein). The allergenic potential of Lyc e 3-deficient tomato fruits was tested by measuring histamine release from sensitized human basophils stimulated with transgenic and parental lines. These assays revealed a strong (10- to 100-fold) decrease in histamine release of human basophils challenged with transgenic fruit extracts when compared with control extracts. These results demonstrate the feasibility of creating low allergenic tomato fruits by means of dsRNAi inhibition.

Specific immunotherapy for food allergy: basic principles and clinical aspects.

PURPOSE OF REVIEW: Food allergy may be life threatening and its management continues to consist of avoiding relevant allergens and, in the case of accidental ingestion, initiation of appropriate emergency therapy. The aim of this article is to describe current treatment approaches and discuss attempts to use specific immunotherapy for food-allergy treatment. RECENT FINDINGS: A recent study reports the use of sublingual immunotherapy for hazelnut food allergy in hazelnut-allergic patients. A significant increase in tolerance to hazelnuts after sublingual immunotherapy as assessed by double-blind, placebo-controlled food challenge, and good tolerance to this treatment, have been observed. SUMMARY: The purpose of this review is to highlight the most promising novel approaches for treating food allergy beyond allergen avoidance. Some of these approaches alone, such as traditional Chinese herbal medicine, anti-immunoglobulin E therapy or sublingual immunotherapy for food allergy, or the combination of different approaches, would probably offer the best treatment option for food-allergic patients in the near future.

[Celecoxib in NSAID-induced cutaneous and respiratory adverse reactions]. / Celecoxib en pacientes con reacciones adversas cutáneas y respiratorias a los antiinflamatorios no esteroideos.

BACKGROUND AND OBJECTIVE: Inhibition of COX-1 appears to be a key event in most non-steroidal anti-inflammatory drugs (NSAIDs)-induced adverse reactions. We evaluated celecoxib tolerance, a highly specific COX-2 inhibitor, in NSAIDs-sensitive patients. PATIENTS AND METHOD: Intolerant patients were challenged in a single-blind study with placebo and celecoxib (increasing doses up to 400 mg). RESULTS: We included 59 patients (41 women): 34 with urticaria with or without angiodema, 21 with bronchospasm, and 4 with urticaria and bronchospasm. Only two patients on celecoxib developed urticaria (3.4%). CONCLUSIONS: Celecoxib is well tolerated by most NSAIDs-intolerant patients and can be a safe alternative when analgesic or antiinflammatory therapy is indicated.

Diagnosis and allergen immunotherapy treatment of polysensitised patients with respiratory allergy in Spain: an Allergists' Consensus.

BACKGROUND: Polysensitisation is common in patients with respiratory allergy in Spain. Selection of the best allergen immunotherapy (AIT) is difficult in polysensitised patients. The present study was designed to help allergists better identify relevant allergens in these patients and to improve the selection of AIT in Spain. METHODS: Sixty-two Spanish allergists answered a survey containing 88 items divided into four groups: 1) general approach to polysensitised subjects; 2) sensitisation profile involving mite, animal dander and moulds; 3) grass and olive pollen co-sensitisation, and 4) other pollen polysensitisation profile (weed and tree pollen). The Delphi method was used. RESULTS: A consensus was achieved for 83% of items (92%, 81%, 83% and 73% of the four groups analysed, respectively). Only polysensitised patients with clinical relevance should be considered polyallergic. A detailed medical history (clinical symptoms and medication) together with a profound knowledge of allergens present in the patient's environment are essential for diagnosis. Skin prick tests (SPTs) are not adequate to decide the clinical relevance of each allergen. Serum specific IgE against allergen sources adds value to SPT but molecular diagnosis, when possible, is strongly recommended, especially in pollen-allergic patients. Specific allergen challenge tests are difficult to perform and not recommended for daily practice. Regarding AIT composition, up to three allergens can be used in the same vaccine, but only related allergens may be mixed. In some cases more than one vaccine may be needed. CONCLUSION: Some criteria have been established to improve diagnosis and AIT prescription in polysensitised patients.

Generation of a comprehensive panel of crustacean allergens from the North Sea Shrimp Crangon crangon.

BACKGROUND: Published data on crustacean allergens are incomplete. The identification of tropomyosin (TM), arginine kinase (AK), sarcoplasmic Ca-binding protein (SCP) and myosin light chain (MLC) as shrimp allergens are all important contributions but additional allergens are required for the development of a complete set of reagents for component resolved diagnosis and the exploration of novel vaccination strategies. METHODS: The North Sea shrimp (Crangon crangon), which is frequently consumed in Europe, served as a model organism in this study. TM and AK were directly cloned from mRNA based on sequence homology and produced as recombinant proteins. Additional IgE-reactive proteins were isolated by preparative SDS-PAGE and identified by mass spectrometry and corresponding cDNAs were cloned and expressed in E. coli. The relevance of the 6 cloned crustacean allergens was confirmed with sera of 31 shrimp-allergic subjects, 12 of which had a positive double-blind, placebo-controlled food challenge (DBPCFC) to shrimp and 19 a convincing history of food allergy to shrimp, including 5 cases of anaphylaxis. Quantitative IgE measurements were performed by ImmunoCAP. RESULTS: Six recombinant crustacean proteins: TM, AK, SCP, a novel MLC, troponin C (TnC), and triosephosphate isomerase (TIM) bound IgE in ImmunoCAP analysis. Specific IgE to at least one of these single shrimp allergens was detected in 90% of the study population, thus the in vitro diagnostic sensitivity was comparable to that of shrimp extract (97%). In 75% of the subjects, the combined technical sensitivity was similar to or greater with single shrimp allergens than with natural shrimp extract. CONCLUSIONS: We identified six IgE-binding proteins from C. crangon, three of which have not before been described as allergens in crustaceans. This extensive panel of shrimp allergens forms a valuable asset for future efforts towards the identification of clinically relevant biomarkers and as a basis to approach patient-tailored immunotherapeutic strategies.

Skin prick tests reveal stable and heritable reduction of allergenic potency of gene-silenced tomato fruits.

BACKGROUND: Today, for patients with food allergy, the only possibility to prevent allergic reactions is avoidance of the allergenic food. Genetic engineering of hypoallergenic plants by means of RNA interference (RNAi) could be an approach to improve the quality of life of subjects with food allergy. OBJECTIVES: We sought to achieve stable inhibition of expression of the allergenic nonspecific lipid transfer protein Lyc e 3 in tomato and to analyze the reduction of allergenicity in vitro by using histamine release assays and in vivo by using skin prick tests with transgenic tomato fruits. METHODS: Gene silencing was performed by means of RNAi and monitored by using Western blotting with nonspecific lipid transfer protein-specific antibodies and sera from patients with tomato allergy. Dose-dependent basophil histamine release assays, prick-to-prick skin testing, and determination of endogenous histamine content were performed with fruits harvested from plants of the first and second generation to assess the allergenic potency compared with that of wild-type fruits. RESULTS: We demonstrated that silencing of Lyc e 3 by means of RNAi contributes to reduced skin reactivity and is passed on to the next generation of fruits. A significant reduction of allergenic potency was determined in vitro and confirmed by using skin prick tests. CONCLUSION: Taken together, these results indicate that RNAi technology is an effective tool to generate foods with reduced allergenicity. CLINICAL IMPLICATIONS: Allergen-reduced plant foods might allow reduction of dietary restrictions for patients allergic to panallergen families.

Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract.

BACKGROUND: Food allergy may be life-threatening, and patients affected need to receive accurate diagnoses and treatment. Hazelnut has often been implicated as responsible for allergic reactions, and trace quantities can induce systemic reactions. OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerance of sublingual immunotherapy with a standardized hazelnut extract in patients allergic to hazelnut. METHODS: This was a randomized, double-blind, placebo-controlled study. Inclusion criteria were a history of hazelnut allergy and positive skin prick test and double-blind placebo-controlled food challenge results. Patients were then randomly assigned into 2 treatment groups (hazelnut immunotherapy or placebo). Efficacy was assessed by double-blind, placebo-controlled food challenge after 8 to 12 weeks of treatment. Blood samples were drawn for measurement of specific IgE, IgG(4), and serum cytokines before and after treatment. RESULTS: Twenty-three patients were enrolled and divided into 2 treatment groups. Twenty-two patients reached the planned maximum dose at 4 days. Systemic reactions were observed in only 0.2% of the total doses administered. Mean hazelnut quantity provoking objective symptoms increased from 2.29 g to 11.56 g (P = .02; active group) versus 3.49 g to 4.14 g (placebo; NS). Moreover, almost 50% of patients who underwent active treatment reached the highest dose (20 g), but only 9% in the placebo. Laboratory data showed an increase in IgG(4) and IL-10 levels after immunotherapy in only the active group. CONCLUSION: Our data confirm significant increases in tolerance to hazelnut after sublingual immunotherapy as assessed by double-blind, placebo-controlled food challenge, and good tolerance to this treatment.