Single-tree nut immunotherapy attenuates allergic reactions in mice with hypersensitivity to multiple tree nuts
BACKGROUND: Allergic reactions to tree nuts are often severe and are outgrown in less than 10% of diagnosed patients. OBJECTIVES: To determine whether treatment of underlying tree nut sensitization will prevent allergic reactions to cross-reacting tree nuts and to determine the effects of single-tree nut immunotherapy on true multi-tree nut sensitization. METHODS: Cross-reactivity model: Cashew-sensitized mice underwent immunotherapy with cashew and were subsequently challenged with cashew and pistachio. Multisensitization model: Cashew plus walnut-sensitized mice were treated with cashew alone; walnut alone; or both cashew and walnut and then underwent challenges to cashew and walnut. Challenges were assessed on the basis of symptoms; changes in body temperature; and mouse mast cell protease-1 release. RESULTS: In the cross-reactivity model; cashew immunotherapy completely prevented allergic reactions on challenges with cashew or the cross-reactive pistachio. In the multisensitization model; mice with cashew plus walnut allergy were significantly protected from anaphylactic reactions on cashew challenge in both the cashew-alone and walnut-alone immunotherapy groups. Results from the walnut challenge demonstrated significantly decreased allergic responses in the walnut immunotherapy group; whereas mice in the cashew immunotherapy group experienced significantly lower symptoms. In the cross-reactivity model; immunotherapy effectively decreased IL-4 and IL-5 production and increased IL-12 relative to placebo while also inducing a 5-fold increase in specific IgG(1). CONCLUSION: Single-tree nut immunotherapy can effectively decrease allergic responses in both the cross-reactivity and multisensitization mouse models. Further studies are needed to determine which single-tree nut immunotherapies will be most effective for specific multi-tree nut allergy profiles.
Enzymatic Treatment of Peanut Kernels to Reduce Allergen Levels.
Abstract: This study investigated the use of enzymatic treatment to reduce peanut allergens in peanut kernels as affect by processing conditions. Two major peanut allergens; Ara h 1 and Ara h 2; were used as indicators of process effectiveness. Enzymatic treatment effectively reduced Ara h 1 and Ara h 2 in roasted peanut kernels by up to 100% under optimal conditions. For instance; treatment of roasted peanut kernels with a-chymotrypsin and trypsin for 1-3 hour significantly increased the solubility of peanut protein while reducing Ara h 1 and Ara h 2 in peanut kernel extracts by 100% and 98%; respectively; based on ELISA readings. Ara h 1 and Ara h 2 levels in peanut protein extracts were inversely correlated with protein solubility in roasted peanut. Blanching of kernels enhanced the effectiveness of enzyme treatment in roasted peanuts but not in raw peanuts. The optimal concentration of enzyme was determined by response surface to be in the range of 0.1-0.2%. No consistent results were obtained for raw peanut kernels since Ara h 1 and Ara h 2 increased in peanut protein extracts under some treatment conditions and decreased in others. Research highlights: Enzymatic treatment of roasted peanut boosted protein solubility & reduced allergens. Blanching of roasted peanut enhanced the efficiency of enzymatic treatment. Enzymatic treatment was less effective in reducing allergens in raw peanut. Postharvest treatment has the potential to produce peanut with reduced allergencity. Absence of allergenic potential in treated peanut needs to be confirmed in-vivo.
Influence of Processing on the Allergenic Properties of Pistachio Nut Assessed in Vitro
Pistachio (Pistacia vera) is a tree nut that has been reported to cause IgE-mediated allergic reactions. This study was undertaken to investigate the distinctions between different cultivars of pistachio nut and the influence of different processing on the IgE-binding capacity of whole pistachio protein extracts. The influence of different processes on allergenicity was investigated using competitive inhibition ELISA and Western blotting assays. The Western blotting results of extracts from pistachio cultivars showed no marked difference among them. The IgE-binding capacity was significantly lower for the protein extract prepared from steam-roasted than from raw and dry-roasted pistachio nuts. The results of sensory evaluation analysis and hedonic rating proved no significant differences in color; taste; flavor; and overall quality of raw; roasted; and steam-roasted pistachio nut treatments. The most significant finding of the present study was the successful reduction of IgE-binding by pistachio extracts using steam-roast processing without any significant changes in sensory quality of product.
Ellagic acid and polyphenolics present in walnut kernels inhibit in vitro human peripheral blood mononuclear cell proliferation and alter cytokine production
Tree nuts; including walnuts; are important elicitors of food allergy. We examined the ability of walnut kernel polyphenolics and purified ellagic acid (EA) to modulate cytokine production and cellular proliferation from stimulated human peripheral blood mononuclear cells (PBMC). IL-13 and TNF-alpha production decreased while no change was observed in IL-4 production. Paradoxically; EA and the walnut polyphenolics all significantly and dose-dependently inhibited stimulated [phytohemagglutin (PHA); alpha-CD3; and phorbol myristate acetate (PMA)/ionomycin] PBMC proliferation while simultaneously increasing IL-2 production. When added at time 0 min and 2 h; EA dose-dependently inhibited PHA-induced proliferation. However; at 30 min and 1 h; low doses of EA (10 and 1 muM) significantly increased proliferation above that of PHA alone; although higher doses led to inhibition. Our data do not support the hypothesis that walnut polyphenolics skew a cytokine response toward Th2 in an in vitro environment. However; immunomodulatory effects are present; including an inhibition of cellular proliferation despite no decrease in IL-4 or IL-2.
Management of nut allergy influences quality of life and anxiety in children and their mothers
Nut allergy is known to impact on the quality of life (QoL) and anxiety of both the allergic child and their parents; but little is known about how the management of food allergy is associated with these variables. To investigate the impact of nut allergy on QoL and anxiety in mothers and children with nut allergy in order to identify management strategies that may influence these factors. Forty-one nut allergic children (age 6-16 yrs) and their mothers completed questionnaires to assess maternal and children's QoL (PedsQL; WHOQOL-BREF; FAQL-PB); anxiety (SCAS; STAI) and perceived stress scale (PSS). Children also completed a nut allergy specific QoL questionnaire. Demographic data; details of previous reactions; test results and management plans were collected using parent-report questionnaires and hospital notes. Children with nut allergy had poorer emotional (p = 0.004); social (p = 0.043); and psychological (p = 0.006) QoL compared to healthy normative data. Maternal and child QoL and anxiety were not influenced by the severity of previous reactions. Mother and child reported lower anxiety (p = 0.043 and p < 0.001 respectively) when the child was prescribed an epinephrine auto-injector. Anxiety was not associated with whether the child carried the auto-injector or whether they strictly avoided traces of nuts in foods. Prescribing auto-injectors is associated with reduced anxiety for food allergic children and their mothers; but is not associated with improved adherence with medical management or reduced risk-taking behavior.
Food Allergy Among Children in the United States
Objectives: The goals were to estimate the prevalence of food allergy and to describe trends in food allergy prevalence and health care use among US children. Methods: A cross-sectional survey of data on food allergy among children <18 years of age; as reported in the 1997-2007 National Health Interview Survey; 2005-2006 National Health and Nutrition Examination Survey; 1993-2006 National Hospital Ambulatory Medical Care Survey and National Ambulatory Medical Care Survey; and 1998-2006 National Hospital Discharge Survey; was performed. Reported food allergies; serum immunoglobulin E antibody levels for specific foods; ambulatory care visits; and hospitalizations were assessed. Results: In 2007; 3.9% of US children <18 years of age had reported food allergy. The prevalence of reported food allergy increased 18% (z = 3.4; P < .01) from 1997 through 2007. In 2005-2006; serum immunoglobulin E antibodies to peanut were detectable for an estimated 9% of US children. Ambulatory care visits tripled between 1993 and 2006 (P < .01). From 2003 through 2006; an estimated average of 317000 food allergy-related; ambulatory care visits per year (95% confidence interval: 195000-438000 visits per year) to emergency and outpatient departments and physician's offices were reported. Hospitalizations with any recorded diagnoses related to food allergy also increased between 1998-2000 and 2004-2006; from an average of 2600 discharges per year to 9500 discharges per year (z = 3.4; P < .01); possibly because of increased use of food allergy V codes. Conclusion: Several national health surveys indicate that food allergy prevalence and/or awareness has increased among US children in recent years.
Food allergy knowledge; attitudes; and beliefs in the United States
BACKGROUND: Members of the general public play a significant role in the well-being of food-allergic children; although little is known about the knowledge; attitudes; and beliefs of food allergy among the public. OBJECTIVE: To provide insight into food allergy knowledge and perceptions among the general US population. METHODS: A national sample of adults was recruited in February 2008 to complete the validated Web-based Chicago Food Allergy Research Survey for the General Public. Findings were analyzed to provide composite/itemized knowledge scores; describe attitudes and beliefs; and examine the effect of prior knowledge/familiarity with food allergy on knowledge; attitudes; and beliefs. RESULTS: A sample of 2;148 respondents was obtained. Participants answered 64.9% (range; 12.5%-100.0%) of knowledge-based items correctly. Strengths were identified in areas related to symptoms/severity and triggers/environmental risks of food allergy. Knowledge was poor concerning the distinction between food allergy and food intolerance; the absence of a cure; and current means to treat food allergy. Higher scores were significantly associated with self-report of prior knowledge/familiarity with food allergy; particularly among those with prior training in food allergy (median increase; 7.9%). Perceptions regarding food allergy were generally well distributed; although respondents tended to minimize the stigma associated with food allergy and to oppose specific food allergy policies in schools. CONCLUSIONS: Increased food allergy knowledge among the general public is needed. Improved public awareness of the challenges faced by food-allergic children may encourage adoption of standardized school policies to keep affected children safe. These efforts are critical for protecting young children with food allergy and avoiding life-threatening anaphylactic reactions.
Identification of two pistachio allergens; Pis v 1 and Pis v 2; belonging to the 2S albumin and 11S globulin family
BACKGROUND: IgE-mediated allergic reactions to pistachio appear to be occurring more frequently; however; little is known about its allergenic proteins. OBJECTIVE: We attempted to identify pistachio allergens and to clone the encoding genes. METHODS: Pistachio proteins were extracted and separated by SDS-PAGE. Immunolabelling was performed with sera from 28 pistachio-allergic individuals. Proteins of interest were further analysed by Edman sequencing and mass spectrometry/mass spectrometry (MS/MS). In parallel; a cDNA library was generated from immature pistachios and screened with primers designed on the basis of internal sequences and peptide spectra. Full-length cDNA clones were isolated from the library and sequenced. Recombinant proteins were expressed and tested with sera from pistachio-allergic patients. RESULTS: Nineteen out of 28 patients (68%) showed IgE binding to a 7 kDa protein fraction; while 14 (50%) showed specific IgE to a 32 kDa protein fraction. Analysis by Edman sequencing and MS/MS revealed that these proteins were homologue to the cashew nut allergens Ana o 3 and Ana o 2; respectively. Screening of the pistachio cDNA library resulted in isolation of novel protein cDNAs. Open-reading frame translation provided the complete amino acid sequences of two new allergenic pistachio proteins. Recombinant proteins were recognized by six out of six selected patients. Therefore; these new allergens were named Pis v 1 and Pis v 2 by the Allergen Nomenclature Subcommittee. CONCLUSION: Novel allergens in pistachio; Pis v 1 and Pis v 2; which belong to 2S albumin and 11S globulin family; respectively; were isolated and the genes encoding these allergens were identified.
Component-resolved in vitro diagnosis of hazelnut allergy in Europe
BACKGROUND: Food allergy to hazelnut occurs both with and without concomitant pollen allergy. OBJECTIVE: We sought to evaluate a panel of hazelnut allergens for diagnosis of hazelnut allergy in Spain; Switzerland; and Denmark. METHODS: Fifty-two patients with a positive double-blind; placebo-controlled food challenge result with hazelnuts; 5 patients with a history of anaphylaxis; 62 patients with pollen allergy but hazelnut tolerance; and 63 nonatopic control subjects were included. Serum IgE levels to hazelnut extract; recombinant hazelnut allergens (rCor a 1.04; rCor a 2; rCor a 8; rCor a 11); and native allergens (nCor a 9; nCor a Bd8K; nCor a Bd11K) were analyzed by means of ImmunoCAP. RESULTS: Among patients with hazelnut allergy; 91% (Switzerland/Spain; 100%; Denmark; 75%) had IgE to hazelnut extract; 75% to rCor a 1.04; 42% to rCor a 2; 28% to rCor a 8; and 2% to rCor a 11. The highest rate of sensitization to Cor a 1.04 was found in the northern regions (Switzerland/Denmark; 100%; Spain; 18%); whereas IgE to the lipid transfer protein rCor a 8 prevailed in Spain (Spain; 71%; Switzerland; 15%; Denmark; 5%). IgE to profilin rCor a 2 was equally distributed (40% to 45%). Among control subjects with pollen allergy; 61% had IgE to hazelnut extract; 69% to rCor a 1.04; 34% to rCor a 2; 10% to rCor a 8; and 6% to rCor a 11. CONCLUSION: Component-resolved in vitro analyses revealed substantial differences in IgE profiles of hazelnut allergic and hazelnut tolerant patients across Europe.
Clinical features of four cases with cashew nut allergy and cross-reactivity between cashew nut and pistachio
BACKGROUND: Few cases of cashew nut (CN) allergy have been reported in Japan. We evaluated the clinical features of 4 cases with CN allergy and investigated the allergens involved. METHODS: In order to investigate the cross-reactivity between CN and pistachios; we performed ImmunoCAP inhibition tests using sera of 4 cases with positive histories of CN allergy and positive results of specific IgE measurement (ImmunoCAP) and skin prick tests. Furthermore; we analyzed the molecular weights of allergens of CN and pistachios by IgE-immunoblotting. RESULTS: Of the 4 cases (male : female = 1:3); there were 3 cases (patient #2-4) and 1 case (patient #1) of anaphylaxis and oral allergy syndrome; respectively. The initial symptom was an oropharyngeal symptom in 3 of the 4 cases; of which 2 cases developed anaphylaxis within 10 minutes after eating only a few pieces of CN. All 4 cases reacted positively to the skin prick test with CN; although 1 case of anaphylaxis tested negatively for CN by ImmunoCAP. Additionally; in 2 cases; IgE-binding to CN and pistachio were inhibited with both pistachios and CN; indicating cross-reactivity between CN and pistachios. IgE-immunoblotting of CN using sera from the 4 cases revealed 2 bands at molecular weights of approximately 33 kd and 42 kd; whereas that of pistachios showed a single band at 36 kd. However; IgE in all 4 sera did not bind to rAna o 2. CONCLUSIONS: In CN allergy; a small amount of CN could induce a severe anaphylactic reaction. Moreover; in cases of suspected CN allergy; reactions to not only CN but also pistachio; which could be cross-reactive to CN; should be examined.