Scope
No accepted and validated methods are currently available which can accurately predict protein allergenicity. In this study, the role of digestion and transport on protein allergenicity is ...investigated.
Methods and results
Peanut allergens (Ara h 1, 2, 3, and 6) and a milk allergen (β‐lactoglobulin) are transported across pig intestinal epithelium using the InTESTine model and afterward basophil activation is measured to assess the (remaining) functional properties. Additionally, allergens are digested by pepsin prior to epithelial transport and their allergenicity is assessed in a human mast cell activation assay. Remarkably, transported Ara h 1 and 3 are not able to activate basophils, in contrast to Ara h 2 and 6. Digestion prior to transport results in a significant increase in mast cell activation of Ara h 1 and 3 dependent on the length of digestion time. Activation of mast cells by Ara h 2 and 6 is unaffected by digestion prior to transport.
Conclusions
Digestion and transport influences the allergenicity of Ara h 1 and 3, but not of Ara h 2 and 6. The influence of digestion and transport on protein allergenicity may explain why current in vitro assays are not predictive for allergenicity.
Current methods for in vitro allergenicity assessment use purified or recombinant proteins to assess allergenicity, which does not mimic the physiological situation. Digestion and epithelial transport affected protein allergenicity. Undigested Ara h 1 and 3 did not elicit reactivity after transport (A) but did when digested prior to transport (B). Ara h 2 and 6 reactivity is not affected.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
The peanut allergens Ara h 2, h 6, and h 7 are potent allergens and can trigger severe reactions. Ara h 7 consists of three isoforms differing in their ability to induce basophil ...degranulation, whereas the ability of Ara h 7.0201 is comparable to Ara h 2 and 6 as shown in previous literature.
Objective
To identify linear epitopes of Ara h 7.0101, Ara h 7.0201 and Ara h 7.0301 recognized by IgE and IgG4 from patients sensitized to Ara h 7 and to investigate their potential to elucidate divergent abilities of the Ara h 7 isoforms in inducing basophil activation.
Methods
Linear epitopes recognized by IgE and IgG4 were mapped by peptide microarray analysis containing 15‐mer peptides of Ara h 2.0201, 6, 7.0101, 7.0201 and 7.0301 and 39 peanut allergic patients sensitized to Ara h 7 (discovery). For validation, 20‐mer peptides containing the minimal epitope and surrounding amino acids were incubated with 25 sensitized patients and 10 controls (validation).
Results
Three out of 14 linear epitopes were unique for each isoform (Ara h 7.0101: aa 97‐109; Ara h 7.0201: aa 122‐133; Ara h 7.0301: aa 65‐74) but scarcely recognized by IgE. The main linear IgE epitope (aa 51‐57) located in the long flexible loop of all Ara h 7 isoforms was bound by antibodies from 31% of the patients (discovery and validation cohort). Regarding IgG4, 55% of the patients recognized an epitope present on all isoforms (aa 55‐65), whereas epitope aa 129‐137, only present on Ara h 7.0101/0.0301, was recognized by 38% of the patients. Recognition was highly individual, although 20% of the patients recognized any linear epitope neither by IgE nor by IgG4 despite a low mean z‐score of ≥ 1.7. Remarkably, only 50% of the patients recognized one or more epitopes by IgE.
Conclusion & Clinical Relevance
Ara h 7 isoforms share many linear epitopes being easily accessible for antibody binding. Unique epitopes, essential to elucidate divergent potencies, were scarcely recognized, suggesting a crucial involvement of conformational epitopes.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Component‐resolved diagnostics (CRD) help predict hazelnut allergy (HA) in children, but are of unknown diagnostic value in adults. This study aimed to evaluate the diagnostic accuracy of ...IgE to hazelnut extract and components in adults.
Methods
A Dutch population of consecutively presenting adults suspected of HA, who underwent a double‐blind placebo‐controlled food challenge, were included. Serum IgE to hazelnut extract and Cor a 1, 8, 9, and 14 was measured on ImmunoCAP. Diagnostic accuracy was assessed by area under the curve (AUC) analysis.
Results
Of 89 patients undergoing challenge, 46 had challenge‐confirmed HA: 17 based on objective and 29 based on subjective symptoms. At commonly applied cutoffs 0.1 and 0.35 kUA/L, high sensitivity was observed for IgE to hazelnut extract and Cor a 1 (range 85–91%), and high specificity for IgE to Cor a 8, 9 and 14 (range 77–95%). However, the AUCs for hazelnut extract and components were too low for accurate prediction of HA (range 0.50–0.56). Combining hazelnut extract and component IgE measurements did not significantly improve accuracy. Higher IgE levels to Cor a 9 and 14 were tentatively associated with HA with objective symptoms, but the corresponding AUCs still only reached 0.68 and 0.63, respectively.
Conclusions
Although hazelnut allergic adults are generally sensitized to hazelnut extract and Cor a 1, and hazelnut tolerant adults are usually not sensitized to Cor a 8, 9, or 14, challenge testing is still needed to accurately discriminate between presence and absence of HA in adults from a birch‐endemic country.
Dutch hazelnut allergic adults are usually sensitized to hazelnut extract and Cor a 1 (sensitivity 85‐91%). Dutch hazelnut tolerant adults are usually not sensitized to Cor a 8, 9, or 14 (specificity 77‐95%). Measurement of IgE to hazelnut allergen components (AUC 50‐56%) cannot replace hazelnut challenge for diagnosis of hazelnut allergy in adults in birch‐endemic regions.Abbreviations: AUC, area under the curve; DBPCFC, double‐blind placebo‐controlled food challenge; HN, hazelnut.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Although hen's egg allergy is more prevalent in children, up to 0.6% of adults from different European countries suffer from a persistent or newly onset hen's egg allergy, making accurate ...diagnosis in adults necessary. However, sensitization to hen's egg extracts, components and linear epitopes is solely studied in children.
Methods
Hen's egg allergic (n = 16) and tolerant (n = 19) adults were selected by sensitization towards recombinant components rGal d 1 and/or 3. Sensitization profiles towards egg white and yolk extract and the native components Gal d 1, 2, 3 and 4 were respectively evaluated with the ImmunoCAP or the EUROLINE system. Characterization of linear epitopes was performed with a peptide microarray containing 15mer peptides representing the entire sequence of mature Gal d 1 and 3.
Results
Overall, sIgE titres against hen's egg extracts and single components overlapped largely between allergic and tolerant adults. Although the median sIgE/sIgG4 ratio to Gal d 1 was increased in allergic adults, the range was comparable between both groups. Clinically relevant sensitization to Gal d 1 was confirmed by sIgE‐binding to the linear epitopes aa30‐41, aa39‐50 or aa84‐95 in 6/13 allergic adults, mainly suffering from objective symptoms. In comparison, these epitopes were recognized by 1/15 tolerant patient. Only a few linear epitopes were detected for Gal d 3, suggesting a greater importance of conformational epitopes for the recognition of Gal d 3.
Conclusion and Clinical Relevance
Specific IgE‐binding to linear epitopes of Gal d 1 is highly specific in identifying hen's egg allergic adults with objective symptoms.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Background Hazelnut allergy is birch pollen–driven in Northern/Western Europe and lipid transfer protein–driven in Spain and Italy. Little is known about other regions and other allergens. Objective ...Establishing a molecular map of hazelnut allergy across Europe. Methods In 12 European cities, subjects reporting reactions to hazelnut (n = 731) were evaluated and sensitization to 24 foods, 12 respiratory allergen sources, and latex was tested by using skin prick test and ImmunoCAP. A subset (124 of 731) underwent a double-blind placebo-controlled food challenge to hazelnut. Sera of 423 of 731 subjects were analyzed for IgE against 7 hazelnut allergens and cross-reactive carbohydrate determinants by ImmunoCAP. Results Hazelnut allergy was confirmed in 70% of those undergoing double-blind placebo-controlled food challenges. Birch pollen–driven hazelnut sensitization (Cor a 1) dominated in most cities, except in Reykjavik, Sofia, Athens, and Madrid, where reporting of hazelnut allergy was less frequent anyhow. In Athens, IgE against Cor a 8 dominated and strongly correlated with IgE against walnut, peach, and apple and against Chenopodium , plane tree, and mugwort pollen. Sensitization to seed storage proteins was observed in less than 10%, mainly in children, and correlated with IgE to nuts, seeds, and legumes. IgE to Cor a 12, observed in all cities (10% to 25%), correlated with IgE to nuts, seeds, and pollen. Conclusions In adulthood, the importance of hazelnut sensitization to storage proteins, oleosin (Cor a 12), and Cor a 8 is diluted by the increased role of birch pollen cross-reactivity with Cor a 1. Cor a 8 sensitization in the Mediterranean is probably driven by diet in combination with pollen exposure. Hazelnut oleosin sensitization is prevalent across Europe; however, the clinical relevance remains to be established.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background
Complex ventral hernia repair is a common operation performed in a diverse population. Post-operatively, patients may have a prolonged length of stay pending facility placement. With ...increasing in-patient volumes, the authors aim to identify risk factors for non-home discharge to expedite placement applications and decrease length of stay.
Methods
The ACS-NSQIP database was queried for all ventral hernia repairs with separation of components performed between 2005 and 2016, excluding patients that left against medical advice or expired. Multivariate logistic regression was performed to identify independent risk factors for discharge to a facility as well as the risk for post-discharge complications following discharge to a facility after univariate analysis to compare demographics, comorbidities, and complications. Independent sample t test was done to compare mean age, body mass index and length of stay.
Results
4549 patients met inclusion criteria. Pre-operative factors significantly associated with non-home discharge on multivariate analysis were female gender, history of diabetes, history of hypertension, older age (60+), presence of pre-operative wound infection/contaminated wound, sepsis, and dependent functional status. Intra-operative factors included ASA classification of 3 or 4 and longer operative time.
Conclusion
Our study was able to identify several predictive factors, mostly pre-operative, that increase the likelihood that a patient will require discharge to a facility after complex ventral hernia repair. Identification of these factors can expedite patient discharge disposition resulting in decreased length of stay, less hospital-acquired conditions, and minimized health care costs.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Food allergy significantly impairs health‐related quality of life (HRQL). Currently, it is still unknown whether diagnostic interventions for food allergy improve HRQL. We aim to assess ...the impact of diagnostic interventions for food allergy on HRQL.
Methods
A systematic search was performed in MEDLINE, Embase, Cochrane Library, and CINAHL focused on patients with a (suspected) food allergy who underwent diagnostic interventions (ie, skin prick test, specific IgE, or oral food challenges OFC) and in whom HRQL was assessed. The mean difference between HRQL before and after the diagnostic intervention was calculated. A minimal clinically important difference of 0.5 was considered clinically relevant for the food allergy quality of life questionnaire.
Results
Seven of 1465 original identified publications were included in which the impact of an OFC on HRQL was investigated (total patients n = 1370). No other diagnostic interventions were investigated. Food allergy‐specific parent‐reported HRQL improved significantly after an OFC irrespective of the outcome in children with a suspected food allergy in two publications. The change was considered clinically relevant in one of two publications. In addition, parent‐reported HRQL improved after an OFC to assess the eliciting dose in children with a confirmed food allergy. The parental burden was significantly reduced after an OFC to assess resolution of food allergy. A meta‐analysis could not be performed due to the limited numbers of, and considerable heterogeneity between, eligible publications.
Conclusion
An OFC is associated with an improved food allergy‐specific HRQL and a reduced parental burden of food allergy.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
PDF
