Walnut Allergy Across Europe: Distribution of Allergen Sensitization Patterns and Prediction of Severity

Background: Walnut allergy is common across the globe, but data on the involvement of individual walnut components are scarce. Objectives: To identify geographical differences in walnut component sensitization across Europe, explore cosensitization and cross-reactivity, and assess associations of clinical and serological determinants with severity of walnut allergy. Methods: As part of the EuroPrevall outpatient surveys in 12 European cities, standardized clinical evaluation was conducted in 531 individuals reporting symptoms to walnut, with sensitization to all known walnut components assessed in 202 subjects. Multivariable Lasso regression was applied to investigate predictors for walnut allergy severity. Results: Birch-pollen-related walnut sensitization (Jug r 5) dominated in Northern and Central Europe and lipid transfer protein sensitization (Jug r 3) in Southern Europe. Profilin sensitization (Jug r 7) was prominent throughout Europe. Sensitization to storage proteins (Jug r 1, 2, 4, and 6) was detected in up to 10% of subjects. The walnut components that showed strong correlations with pollen and other foods differed between centers. The combination of determinants best predicting walnut allergy severity were symptoms upon skin contact with walnut, atopic dermatitis (ever), family history of atopic disease, mugwort pollen allergy, sensitization to cat or dog, positive skin prick test result to walnut, and IgE to Jug r 1, 5, 7, or carbohydrate determinants (area under the curve = 0.81; 95% CI, 0.73-0.89). Conclusions: Walnut-allergic subjects across Europe show clear geographical differences in walnut component sensitization and cosensitization patterns. A predictive model combining results from component-based serology testing with results from extract-based testing and information on clinical background allows for good discrimination between mild to moderate and severe walnut allerg

Influence of sex and phenotype on cardiac outcomes in patients with Fabry disease

Objective: This study describes the influence of sex and disease phenotype on the occurrence of cardiac events in Fabry disease (FD). Methods: Cardiac events from birth to last visit (median age 50 years) were recorded for 213 patients with FD. Patients were categorised as follows: men with classical FD (n=57), men with non-classical FD (n=26), women with classical FD (n=98) and women with non-classical FD (n=32), based on the presence of classical FD symptoms, family history (men and women), biomarkers and residual enzyme activity (men). Event rates per 1000 patient-years after the age of 15 years and median event-free survival (EVS) age were presented. Influence of disease phenotype, sex and their interaction was studied using Firth's penalised Cox regression. Results: The event rates of major cardiovascular events (combined endpoint cardiovascular death (CVD), heart failure (HF) hospitalisation, sustained ventricular arrhythmias (SVAs) and myocardial infarction) were 11.0 (95% CI 6.6 to 17.3) in men with classical FD (EVS 55 years), 4.4 (95% CI 2.5 to 7.1) in w

Hazelnut allergy across Europe dissected molecularly: a EuroPrevall outpatient clinic survey

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

Ratios of specific IgG4 over IgE antibodies do not improve prediction of peanut allergy nor of its severity compared to specific IgE alone

Background: IgG4 antibodies have been suggested to play a protective role in the translation of peanut sensitization into peanut allergy. Whether they have added value as diagnostic read-out has not yet been reported. Objective: To evaluate whether (a) peanut-specific IgG, IgG4 and/or IgA antibodies are associated with tolerance and/or less severe reactions and (b) they can improve IgE-based diagnostic tests. Methods: Sera of 137 patients with challenge-proven peanut allergy and of 25 subjects that tolerated peanut, both with known IgE profiles to peanut extract and five individual peanut allergens, were analyzed for specific IgG and IgG4. Antibody levels and ratios thereof were associated with challenge outcome including symptom severity grades. For comparison of the discriminative performance, receiver operating characteristic curve (ROC) analysis was used. Results: IgE against Ara h 2 was significantly higher in allergic than in tolerant patients and associated with severity of reactions (P < 0.001) with substantial diagnostic capability (AUC 0.91, 95%CI 0.87-0.96 and 0.80, 95%CI 0.73-0.87, respectively). IgG and IgG4 were also positively associated albeit significantly weaker (AUCs from 0.65 to 0.72). On the other hand, ratios of IgG and IgG4 over IgE were greater in patients that were tolerant or had mild symptoms as compared to severe patients but they did not predict challenge outcomes better than IgE alone (AUCs from 0.54 to 0.89). Conclusion: IgE against Ara h 2 is the best biomarker for predicting peanut challenge outcomes including severity and IgG and IgG4 antibody ratios over IgE do not improve these outcomes

ECG Changes during Adult Life in Fabry Disease: Results from a Large Longitudinal Cohort Study

Background: Fabry disease (FD) is an X-linked, lysosomal storage disorder leading to severe cardiomyopathy in a significant proportion of patients. To identify ECG markers that reflect early cardiac involvement and disease progression, we conducted a long term retrospective study in a large cohort of FD patients. Methods: A total of 1995 ECGs from 133 patients with classical FD (64% females, 80% treated with enzyme replacement therapy), spanning 20 years of follow-up, were compared to ECGs from 3893 apparently healthy individuals. Generalized linear mixed models were used to evaluate the effect of age, FD and sex on: P-wave duration, PR-interval, QRS-duration, QTc, Cornell index, spatial QRS-T angle and frontal QRS-axis. Regression slopes and absolute values for each parameter were compared between FD patients and control subjects. Results: At a younger age (<40 years), the Cornell index was higher and frontal QRS-axis more negative in FD patients compared to controls (p < 0.05). For the other ECG parameters, the rate of change, more than the absolute value, was greater in FD patients compared to controls (p < 0.05). From the fifth decade (men) or sixth (women) onwards, absolute values for P-wave duration, QRS-duration, QTc and spatial QRS-T angle were longer and higher in FD patients compared to control subjects. Conclusions: ECG abnormalities indicative of FD are age and sex dependent. Tracking the rate of change in ECG parameters could be a good way to detect disease progression, guiding treatment initiation. Moreover, monitoring ECG changes in FD can be used to evaluate the effectiveness of treatment

Hazelnut allergy across Europe dissected molecularly: A EuroPrevall outpatient clinic survey.

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.Establishing a molecular map of hazelnut allergy across Europe.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.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.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.info:eu-repo/grantAgreement/EC/FP7/ 31214

Estimating the Risk of Severe Peanut Allergy Using Clinical Background and IgE Sensitization Profiles

BACKGROUND: It is not well-understood why symptom severity varies between patients with peanut allergy (PA). OBJECTIVE: To gain insight into the clinical profile of subjects with mild-to-moderate and severe PA, and investigate individual and collective predictive accuracy of clinical background and IgE to peanut extract and components for PA severity. METHODS: Data on demographics, patient history and sensitization at extract and component level of 393 patients with probable PA (symptoms ≤ 2 h + IgE sensitization) from 12 EuroPrevall centers were analyzed. Univariable and penalized multivariable regression analyses were used to evaluate risk factors and biomarkers for severity. RESULTS: Female sex, age at onset of PA, symptoms elicited by skin contact with peanut, family atopy, atopic dermatitis, house dust mite and latex allergy were independently associated with severe PA; birch pollen allergy with mild-to-moderate PA. The cross-validated AUC of all clinical background determinants combined (0.74) was significantly larger than the AUC of tests for sensitization to extract (0.63) or peanut components (0.54–0.64). Although larger skin prick test wheal size, and higher IgE to peanut extract, Ara h 1 and Ara h 2/6, were associated with severe PA, and higher IgE to Ara h 8 with mild-to-moderate PA, addition of these measurements of sensitization to the clinical background model did not significantly improve the AUC. CONCLUSIONS: Models combining clinical characteristics and IgE sensitization patterns can help establish the risk of severe reactions for peanut allergic patients, but clinical background determinants are most valuable for predicting severity of probable PA in an individual patient

Walnut Allergy Across Europe:Distribution of Allergen Sensitization Patterns and Prediction of Severity

Background: Walnut allergy is common across the globe, but data on the involvement of individual walnut components are scarce. Objectives: To identify geographical differences in walnut component sensitization across Europe, explore cosensitization and cross-reactivity, and assess associations of clinical and serological determinants with severity of walnut allergy. Methods: As part of the EuroPrevall outpatient surveys in 12 European cities, standardized clinical evaluation was conducted in 531 individuals reporting symptoms to walnut, with sensitization to all known walnut components assessed in 202 subjects. Multivariable Lasso regression was applied to investigate predictors for walnut allergy severity. Results: Birch-pollen–related walnut sensitization (Jug r 5) dominated in Northern and Central Europe and lipid transfer protein sensitization (Jug r 3) in Southern Europe. Profilin sensitization (Jug r 7) was prominent throughout Europe. Sensitization to storage proteins (Jug r 1, 2, 4, and 6) was detected in up to 10% of subjects. The walnut components that showed strong correlations with pollen and other foods differed between centers. The combination of determinants best predicting walnut allergy severity were symptoms upon skin contact with walnut, atopic dermatitis (ever), family history of atopic disease, mugwort pollen allergy, sensitization to cat or dog, positive skin prick test result to walnut, and IgE to Jug r 1, 5, 7, or carbohydrate determinants (area under the curve = 0.81; 95% CI, 0.73-0.89). Conclusions: Walnut-allergic subjects across Europe show clear geographical differences in walnut component sensitization and cosensitization patterns. A predictive model combining results from component-based serology testing with results from extract-based testing and information on clinical background allows for good discrimination between mild to moderate and severe walnut allergy

Development and validation of the Food Allergy Severity Score.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBackground: The heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions. Methods: Following a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best-Worst Scaling of 32 food reactions was calculated. Results: oFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC-AUC]>0.80), classification (sensitivity 0.87-0.92, specificity 0.73-0.78), and calibration. Bootstrapping over ROC-AUC showed negligible biases (1.0 × 10-6 -1.23 × 10-3 ). In external validation, nFASS performed best with higher ROC-AUC. nFASS was strongly correlated (R 0.89) to best-worst scoring of 334 expert clinicians. Conclusion: FASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings. Keywords: allergic reactions; anaphylaxis; food allergy; score; severity.European Commission BIOGRIAL-SEVERAL project ARADyAL Research Networ