Research

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10 pages, 887 KiB

Open AccessArticle

May Failure to Thrive in Infants Be a Clinical Marker for the Early Diagnosis of Cow’s Milk Allergy?

by Lucia Diaferio, Davide Caimmi, Maria Carmen Verga, Valentina Palladino, Lorenzo Trovè, Paola Giordano, Elvira Verduci and Vito Leonardo Miniello

Nutrients 2020, 12(2), 466; https://doi.org/10.3390/nu12020466 - 13 Feb 2020

Cited by 14 | Viewed by 4184

Abstract

Objectives—Failure to thrive (FTT) in infants is characterized by growth failure. Although, cow’s milk allergy (CMA) may have an impact on growth and leads to FTT, data are still limited. We focused on FTT as a possible clinical marker for an early diagnosis [...] Read more.

Objectives—Failure to thrive (FTT) in infants is characterized by growth failure. Although, cow’s milk allergy (CMA) may have an impact on growth and leads to FTT, data are still limited. We focused on FTT as a possible clinical marker for an early diagnosis of CMA. The aim of the present study was to evaluate the implications of cow’s milk hypersensitivity in infants with FTT and the growth catch-up after a cow’s milk-free diet (CMFD). Methods—A cross-sectional study of all consecutive infants evaluated at the Pediatric Nutrition and Allergy Unit of the University Hospital of Bari (Italy) from January 2016 to April 2018 with a medical-driven diagnosis of FTT. Eligible infants were investigated for possible IgE mediated or non-IgE mediated CMA. Results—43 infants were included, mean age 5.7 months. 33/43 (77%) FTT presented a CMA related disease: 3/43 (7%) were diagnosed as presenting an IgE mediated CMA, 30 (93%) had a non IgE-mediated CMA, confirmed by the elimination diet for diagnostic purposes, that led to a significant improvement of symptoms and recrudescence after milk reintroduction. A total of 29 out of 30 patients (one patient was lost at follow-up) moved up to their original growth percentile after dietary changes. Growth z-scores were computed based on WHO anthropometric data. In 10 out of 43 patients (23%) were diagnosed with gastro-esophageal reflux disease (GERD). Conclusions—when evaluating an infant with FTT, physicians should include in their evaluation an extensive search for IgE mediated and non IgE mediated CMA. When in vivo and in vitro analysis are not conclusive, a 4- to 8-weeks trial of CMFD and a consecutive re-introduction of milk proteins may be helpful in less common diagnoses. Full article

(This article belongs to the Special Issue Contributions of Diet and Gastrointestinal Digestion to Food Allergy)

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17 pages, 1210 KiB

Open AccessArticle

A Comprehensive Peptidomic Approach to Characterize the Protein Profile of Selected Durum Wheat Genotypes: Implication for Coeliac Disease and Wheat Allergy

by Rosa Pilolli, Agata Gadaleta, Luigia Di Stasio, Antonella Lamonaca, Elisabetta De Angelis, Domenica Nigro, Maria De Angelis, Gianfranco Mamone and Linda Monaci

Nutrients 2019, 11(10), 2321; https://doi.org/10.3390/nu11102321 - 01 Oct 2019

Cited by 10 | Viewed by 3280

Abstract

The wheat varietal selection undertaken by breeders in recent decades has been tailored mainly to improve technological and productivity-related traits; however, the latter has resulted in a considerable impoverishment of the genetic diversity of wheat-based products available on the market. This pitfall has [...] Read more.

The wheat varietal selection undertaken by breeders in recent decades has been tailored mainly to improve technological and productivity-related traits; however, the latter has resulted in a considerable impoverishment of the genetic diversity of wheat-based products available on the market. This pitfall has encouraged researchers to revalue the natural diversity of cultivated and non-cultivated wheat genotypes in light of their different toxic/immunogenic potential for celiac disease and wheat-allergic patients. In the present investigation, an advanced proteomic approach was designed for the global characterization of the protein profile of selected tetraploid wheat genotypes (Triticum turgidum). The approach combined proteins/peptides sequence information retrieved by specific enzymatic digestions (single and dual proteolytic enzymes) with protein digestibility information disclosed by means of in-vitro simulated human gastroduodenal digestion experiments. In both cases, the peptide pools were characterized by discovery analysis with liquid chromatography high-resolution tandem mass spectrometry, and specific amino acid sequences were identified via commercial software. The peptide list was screened for in silico toxicity/immunogenicity risk assessment, with the aid of various open-source bioinformatics tools for epitopes matching. Given the global information provided by the designed proteomic approach, the in silico risk assessment not only tackled toxicity implication for celiac disease patients, but also scouted for immunogenic sequences relevant for wheat allergic patients, achieving a comprehensive characterization of the protein profile of the selected genotypes. These latter were assessed to encrypt a variable number of toxic/immunogenic epitopes for celiac disease and wheat allergy, and as such they could represent convenient bases for breeding practices and for the development of new detoxification strategies. Full article

(This article belongs to the Special Issue Contributions of Diet and Gastrointestinal Digestion to Food Allergy)

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12 pages, 1224 KiB

Open AccessArticle

Mouse Chow Composition Influences Immune Responses and Food Allergy Development in a Mouse Model

by Eleonore Weidmann, Nazanin Samadi, Martina Klems, Denise Heiden, Klara Seppova, Davide Ret and Eva Untersmayr

Nutrients 2018, 10(11), 1775; https://doi.org/10.3390/nu10111775 - 16 Nov 2018

Cited by 8 | Viewed by 4239

Abstract

Our diet is known to substantially influence the immune response not only by support of mucosal barriers but also via direct impact on immune cells. Thus, it was of great interest to compare the immunological effect of two mouse chows with substantial differences [...] Read more.

Our diet is known to substantially influence the immune response not only by support of mucosal barriers but also via direct impact on immune cells. Thus, it was of great interest to compare the immunological effect of two mouse chows with substantial differences regarding micro-, macronutrient, lipid and vitamin content on the food allergic response in our previously established mouse model. As the two mouse chows of interest, we used a soy containing feed with lower fatty acid (FA) amount (soy-containing feed) and compared it to a soy free mouse chow (soy-free feed) in an established protocol of oral immunizations with Ovalbumin (OVA) under gastric acid suppression. In the animals receiving soy-containing feed, OVA-specific IgE, IgG1, IgG2a antibody levels were significantly elevated and food allergy was evidenced by a drop of body temperature after oral immunizations. In contrast, mice on soy-free diet had significantly higher levels of IL-10 and were protected from food allergy development. In conclusion, soy-containing feed was auxiliary during sensitizations, while soy-free feed supported oral tolerance development and food allergy prevention. Full article

(This article belongs to the Special Issue Contributions of Diet and Gastrointestinal Digestion to Food Allergy)

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20 pages, 2048 KiB

Open AccessArticle

Heat and Pressure Treatments on Almond Protein Stability and Change in Immunoreactivity after Simulated Human Digestion

by Elisabetta De Angelis, Simona L. Bavaro, Graziana Forte, Rosa Pilolli and Linda Monaci

Nutrients 2018, 10(11), 1679; https://doi.org/10.3390/nu10111679 - 05 Nov 2018

Cited by 30 | Viewed by 4398

Abstract

Almond is consumed worldwide and renowned as a valuable healthy food. Despite this, it is also a potent source of allergenic proteins that can trigger several mild to life-threatening immunoreactions. Food processing proved to alter biochemical characteristics of proteins, thus affecting the respective [...] Read more.

Almond is consumed worldwide and renowned as a valuable healthy food. Despite this, it is also a potent source of allergenic proteins that can trigger several mild to life-threatening immunoreactions. Food processing proved to alter biochemical characteristics of proteins, thus affecting the respective allergenicity. In this paper, we investigated the effect of autoclaving, preceded or not by a hydration step, on the biochemical and immunological properties of almond proteins. Any variation in the stability and immunoreactivity of almond proteins extracted from the treated materials were evaluated by total protein quantification, Enzyme Linked Immunosorbent Assay (ELISA), and protein profiling by electrophoresis-based separation (SDS-PAGE). The sole autoclaving applied was found to weakly affect almond protein stability, despite what was observed when hydration preceded autoclaving, which resulted in a loss of approximately 70% of total protein content compared to untreated samples, and a remarkable reduction of the final immunoreactivity. The final SDS-PAGE protein pattern recorded for hydrated and autoclaved almonds disclosed significant changes. In addition, the same samples were further submitted to human-simulated gastro-intestinal (GI) digestion to evaluate potential changes induced by these processing methods on allergen digestibility. Digestion products were identified by High Pressure Liquid Chromatography-High Resolution Tandem Mass Spectrometry (HPLC-HRMS/MS) analysis followed by software-based data mining, and complementary information was provided by analyzing the proteolytic fragments lower than 6 kDa in size. The autoclave-based treatment was found not to alter the allergen digestibility, whereas an increased susceptibility to proteolytic action of digestive enzymes was observed in almonds subjected to autoclaving of prehydrated almond kernels. Finally, the residual immunoreactivity of the GI-resistant peptides was in-silico investigated by bioinformatic tools. Results obtained confirm that by adopting both approaches, no epitopes associated with known allergens survived, thus demonstrating the potential effectiveness of these treatments to reduce almond allergenicity. Full article

(This article belongs to the Special Issue Contributions of Diet and Gastrointestinal Digestion to Food Allergy)

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14 pages, 1517 KiB

Open AccessArticle

Legume Protein Consumption and the Prevalence of Legume Sensitization

by Mark Smits, Thuy-My Le, Paco Welsing, Geert Houben, André Knulst and Kitty Verhoeckx

Nutrients 2018, 10(10), 1545; https://doi.org/10.3390/nu10101545 - 19 Oct 2018

Cited by 17 | Viewed by 5014

Abstract

Sensitization and allergy to legumes can be influenced by different factors, such as exposure, geographical background, and food processing. Sensitization and the allergic response to legumes differs considerably, however, the reason behind this is not yet fully understood. The aim of this study [...] Read more.

Sensitization and allergy to legumes can be influenced by different factors, such as exposure, geographical background, and food processing. Sensitization and the allergic response to legumes differs considerably, however, the reason behind this is not yet fully understood. The aim of this study is to investigate if there is a correlation between legume protein consumption and the prevalence of legume sensitization. Furthermore, the association between sensitization to specific peanut allergens and their concentration in peanut is investigated. Legume sensitization data (peanut, soybean, lupin, lentil, and pea) from studies were analyzed in relation to consumption data obtained from national food consumption surveys using the European Food Safety Authority (EFSA), Global Environment Monitoring System (GEMS), and What We Eat in America—Food Commodity Intake Database (WWEIA-FCID) databases. Data were stratified for children <4 years, children 4–18 years, and adults. Sufficient data were available for peanut to allow for statistical analysis. Analysis of all age groups together resulted in a low correlation between peanut sensitization and relative peanut consumption (r = 0.407), absolute peanut consumption (r = 0.468), and percentage of peanut consumers (r = 0.243). No correlation was found between relative concentrations of Ara h 1, 2, 3, 6, 7, and 8 in peanut and sensitization to these peanut allergens. The results indicate that the amount of consumption only plays a minor role in the prevalence of sensitization to peanut. Other factors, such as the intrinsic properties of the different proteins, processing, matrix, frequency, timing and route of exposure, and patient factors might play a more substantial role in the prevalence of peanut sensitization. Full article

(This article belongs to the Special Issue Contributions of Diet and Gastrointestinal Digestion to Food Allergy)

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13 pages, 2947 KiB

Open AccessArticle

Release of Major Peanut Allergens from Their Matrix under Various pH and Simulated Saliva Conditions—Ara h2 and Ara h6 Are Readily Bio-Accessible

by Stef J. Koppelman, Mieke Smits, Monic Tomassen, Govardus A.H. De Jong, Joe Baumert, Steve L. Taylor, Renger Witkamp, Robert Jan Veldman, Raymond Pieters and Harry Wichers

Nutrients 2018, 10(9), 1281; https://doi.org/10.3390/nu10091281 - 11 Sep 2018

Cited by 13 | Viewed by 5193

Abstract

The oral mucosa is the first immune tissue that encounters allergens upon ingestion of food. We hypothesized that the bio-accessibility of allergens at this stage may be a key determinant for sensitization. Light roasted peanut flour was suspended at various pH in buffers [...] Read more.

The oral mucosa is the first immune tissue that encounters allergens upon ingestion of food. We hypothesized that the bio-accessibility of allergens at this stage may be a key determinant for sensitization. Light roasted peanut flour was suspended at various pH in buffers mimicking saliva. Protein concentrations and allergens profiles were determined in the supernatants. Peanut protein solubility was poor in the pH range between 3 and 6, while at a low pH (1.5) and at moderately high pHs (>8), it increased. In the pH range of saliva, between 6.5 and 8.5, the allergens Ara h2 and Ara h6 were readily released, whereas Ara h1 and Ara h3 were poorly released. Increasing the pH from 6.5 to 8.5 slightly increased the release of Ara h1 and Ara h3, but the recovery remained low (approximately 20%) compared to that of Ara h2 and Ara h6 (approximately 100% and 65%, respectively). This remarkable difference in the extraction kinetics suggests that Ara h2 and Ara h6 are the first allergens an individual is exposed to upon ingestion of peanut-containing food. We conclude that the peanut allergens Ara h2 and Ara h6 are quickly bio-accessible in the mouth, potentially explaining their extraordinary allergenicity. Full article

(This article belongs to the Special Issue Contributions of Diet and Gastrointestinal Digestion to Food Allergy)

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15 pages, 1310 KiB

Open AccessArticle

Effect of the Strawberry Genotype, Cultivation and Processing on the Fra a 1 Allergen Content

by Elisabeth Kurze, Vanessa Kock, Roberto Lo Scalzo, Klaus Olbricht and Wilfried Schwab

Nutrients 2018, 10(7), 857; https://doi.org/10.3390/nu10070857 - 02 Jul 2018

Cited by 13 | Viewed by 13071

Abstract

Birch pollen allergic patients show cross-reactivity to vegetables and fruits, including strawberries (Fragaria × ananassa). The objective of this study was to quantify the level of the Fra a 1 protein, a Bet v 1-homologous protein in strawberry fruits by a [...] Read more.

Birch pollen allergic patients show cross-reactivity to vegetables and fruits, including strawberries (Fragaria × ananassa). The objective of this study was to quantify the level of the Fra a 1 protein, a Bet v 1-homologous protein in strawberry fruits by a newly developed ELISA, and determine the effect of genotype, cultivation and food processing on the allergen amount. An indirect competitive ELISA using a specific polyclonal anti-Fra a 1.02 antibody was established and revealed high variability in Fra a 1 levels within 20 different genotypes ranging from 0.67 to 3.97 µg/g fresh weight. Mature fruits of red-, white- and yellow-fruited strawberry cultivars showed similar Fra a 1 concentrations. Compared to fresh strawberries, oven and solar-dried fruits contained slightly lower levels due to thermal treatment during processing. SDS-PAGE and Western blot analysis demonstrated degradation of recombinant Fra a 1.02 after prolonged (>10 min) thermal treatment at 99 °C. In conclusion, the genotype strongly determined the Fra a 1 quantity in strawberries and the color of the mature fruits does not relate to the amount of the PR10-protein. Cultivation conditions (organic and conventional farming) do not affect the Fra a 1 level, and seasonal effects were minor. Full article

(This article belongs to the Special Issue Contributions of Diet and Gastrointestinal Digestion to Food Allergy)

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11 pages, 2320 KiB

Open AccessArticle

Immunological Comparison of Native and Recombinant Hen’s Egg Yolk Allergen, Chicken Serum Albumin (Gal d 5), Produced in Kluveromyces lactis

by Chamika De Silva, Pathum Dhanapala, Samuel King, Timothy Doran, Mimi Tang and Cenk Suphioglu

Nutrients 2018, 10(6), 757; https://doi.org/10.3390/nu10060757 - 12 Jun 2018

Cited by 10 | Viewed by 4600

Abstract

Chicken serum albumin (CSA) is a hen’s egg yolk allergen causing IgE-mediated allergy. The objective of this study was to produce a recombinant version of CSA and compare its IgE reactivity to natural CSA (nCSA). CSA was cloned and expressed as a soluble [...] Read more.

Chicken serum albumin (CSA) is a hen’s egg yolk allergen causing IgE-mediated allergy. The objective of this study was to produce a recombinant version of CSA and compare its IgE reactivity to natural CSA (nCSA). CSA was cloned and expressed as a soluble fraction in the yeast Kluyveromyces lactis (K. lactis) protein expression system. The gene encoding CSA was amplified with a C-terminal hemagglutinin epitope tag by polymerase chain reaction (PCR) and cloned into the pKLAC2 expression vector prior to transforming into K. lactis. Recombinant CSA (rCSA) was purified by immunoprecipitation. Twenty-one patients allergic to hen’s egg white were examined for sensitisation against nCSA. 38% of patients were found to be sensitised to CSA based on Western immunoassay. Immunoglobulin E (IgE) binding capacity of rCSA and nCSA was analysed by ELISA using sera from patients sensitised to CSA. Levels of IgE-binding were similar for both the recombinant and the natural CSA, indicating the existence of similar epitopes. rCSA produced in this study is a potential candidate to be used in component-resolved diagnosis (CRD) of egg yolk allergy. The usefulness of rCSA in CRD of egg yolk allergy warrants further characterisation using sera from patients with allergy to hen’s egg yolk in future studies. Full article

(This article belongs to the Special Issue Contributions of Diet and Gastrointestinal Digestion to Food Allergy)

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12 pages, 870 KiB

Open AccessArticle

by Jennifer L. P. Protudjer, Ola Olén, Mirja Vetander, Inger Kull, Erik Melén, Marianne Van Hage, Magnus Wickman and Anna Bergström

Nutrients 2018, 10(5), 651; https://doi.org/10.3390/nu10050651 - 21 May 2018

Cited by 5 | Viewed by 4046

Abstract

Cow’s milk often causes symptoms in infants. Whereas, some continue to experience symptoms through childhood, others become tolerant. Yet, the ages at which persistence and tolerance occur are less clear. Thus, we examined the age of onset and persistence of milk-related symptoms from [...] Read more.

Cow’s milk often causes symptoms in infants. Whereas, some continue to experience symptoms through childhood, others become tolerant. Yet, the ages at which persistence and tolerance occur are less clear. Thus, we examined the age of onset and persistence of milk-related symptoms from early life to adolescence, and Immunoglobulin E (IgE) milk reactivity, focusing on gender differences in a large, population-based birth cohort. Overall, 20.0% (537/2985) of children, with a comparable gender distribution, had early life milk-related symptoms. At 16y, approximately 2% (62/2985) children had persistent symptoms and high milk IgE levels (e.g., median at 4 years: 1.5 kU_A/L) that were beginning in early life. In contrast, 94% had transient symptoms and low median IgE levels (early life: 0.63 kU_A/L, 8y: 0.72 kU_A/L; 16 years: 1.1 kU_A/L). Also, at 16 years, approximately 6% of females and 3% of males without any previously reported symptoms reported adolescent-onset of symptoms (p < 0.001). Such symptoms were almost exclusively gastrointestinal symptoms and were not associated with detectable IgE. In conclusion, early life milk-related symptoms are common, although most cases are transient by 16 years. Twice as many females vs. males report adolescent-onset symptoms, and particularly gastrointestinal symptoms. Children with persistent symptoms have both a higher prevalence and higher milk IgE levels, as compared to other phenotypes. Full article

(This article belongs to the Special Issue Contributions of Diet and Gastrointestinal Digestion to Food Allergy)

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Review

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12 pages, 280 KiB

Open AccessReview

Almond Allergy: An Overview on Prevalence, Thresholds, Regulations and Allergen Detection

by Giuseppina Mandalari and Alan R. Mackie

Nutrients 2018, 10(11), 1706; https://doi.org/10.3390/nu10111706 - 08 Nov 2018

Cited by 23 | Viewed by 6374

Abstract

Food allergy has been on the increase for many years. The prevalence of allergy to different foods varies widely depending on type of food, frequency of consumption and geographic location. Data from the literature suggests that the prevalence of tree nut allergy is [...] Read more.

Food allergy has been on the increase for many years. The prevalence of allergy to different foods varies widely depending on type of food, frequency of consumption and geographic location. Data from the literature suggests that the prevalence of tree nut allergy is of the order of 1% in the general population. Almond is one such tree nut that is frequently eaten in many parts of the world and represents a potential allergenic hazard. Given the need to label products that contain allergens, a number of different methods of direct and indirect detection have been developed. However, in the absence of population-based threshold data, and given that almond allergy is rare, the sensitivity of the required detection is unknown and thus aims as low as possible. Typically, this is less than 1 ppm, which matches the thresholds that have been shown for other allergens. This review highlights the lack of quantitative data on prevalence and thresholds for almonds, which is limiting progress in consumer protection. Full article

(This article belongs to the Special Issue Contributions of Diet and Gastrointestinal Digestion to Food Allergy)

20 pages, 1065 KiB

Open AccessReview

Dietary Interventions in Pollen-Related Food Allergy

by Sarah A. Lyons, Anne M. van Dijk, André C. Knulst, Eleonora Alquati, Thuy-My Le and Harmieke Van Os-Medendorp

Nutrients 2018, 10(10), 1520; https://doi.org/10.3390/nu10101520 - 16 Oct 2018

Cited by 8 | Viewed by 4330

Abstract

In practice, it remains unclear what the best dietary approach is in subjects with pollen-related food allergy (PRFA). Our objective was to evaluate the effect of (1) dietary avoidance advice, (2) oral immunotherapy (OIT), (3) (heat) processing, and (4) consumption of hypoallergenic cultivars [...] Read more.

In practice, it remains unclear what the best dietary approach is in subjects with pollen-related food allergy (PRFA). Our objective was to evaluate the effect of (1) dietary avoidance advice, (2) oral immunotherapy (OIT), (3) (heat) processing, and (4) consumption of hypoallergenic cultivars on frequency, severity, and eliciting dose of pollen-related food allergic reactions. A systematic search was conducted in PubMed, Embase, and Cochrane. All studies performing an in vivo investigation of one of the four interventions in adults with PRFA were included. Each study was assessed for quality and validity. Available data on frequency, severity, and eliciting dose of allergic reactions were extracted. Ten studies matched the eligibility criteria. No studies were retrieved on dietary avoidance advice. Two studies (N = 92) on apple OIT reported that tolerance was induced in 63% and 81% of subjects. Four studies (total N = 116) focused on heat processing. Heating was found to completely eradicate symptoms in 15–71% of hazelnut allergic and 46% of celery allergic individuals. Four studies (N = 60) comparing low to high allergenic apple cultivars revealed that Santana (and possibly Elise) apples seemed to cause milder reactions than Golden Delicious. In the awareness that overall level of evidence was low, we conclude that OIT, heat processing, and hypoallergenic cultivars may diminish or completely prevent allergic reactions in some but not all subjects with PRFA. Full article

(This article belongs to the Special Issue Contributions of Diet and Gastrointestinal Digestion to Food Allergy)

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16 pages, 520 KiB

Open AccessReview

The Effect of Digestion and Digestibility on Allergenicity of Food

by Isabella Pali-Schöll, Eva Untersmayr, Martina Klems and Erika Jensen-Jarolim

Nutrients 2018, 10(9), 1129; https://doi.org/10.3390/nu10091129 - 21 Aug 2018

Cited by 50 | Viewed by 6939

Abstract

Food allergy prevalence numbers are still on the rise. Apart from environmental influences, dietary habits, food availability and life-style factors, medication could also play a role. For immune tolerance of food, several contributing factors ensure that dietary compounds are immunologically ignored and serve [...] Read more.

Food allergy prevalence numbers are still on the rise. Apart from environmental influences, dietary habits, food availability and life-style factors, medication could also play a role. For immune tolerance of food, several contributing factors ensure that dietary compounds are immunologically ignored and serve only as source for energy and nutrient supply. Functional digestion along the gastrointestinal tract is essential for the molecular breakdown and a prerequisite for appropriate uptake in the intestine. Digestion and digestibility of carbohydrates and proteins thus critically affect the risk of food allergy development. In this review, we highlight the influence of amylases, gastric acid- and trypsin-inhibitors, as well as of food processing in the context of food allergenicity. Full article

(This article belongs to the Special Issue Contributions of Diet and Gastrointestinal Digestion to Food Allergy)

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