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Background: Allergic rhinitis and asthma are highly prevalent chronic inflammatory diseases leading to restrictions in the patient's quality of life and high costs for healthcare systems. Both diseases are associated with the presence of specific IgE (sIgE) against aeroallergens. This review aims to examine the importance of molecular allergy diagnostics in the assessment and management of these disorders., Content: The "U-shaped" approach, proposed by the European Academy of Allergy and Clinical Immunology, combines conventional allergy diagnostics with the benefits of component-resolved diagnosis (CRD) and offers important additional information regarding the patient's sensitization pattern, especially in complex clinical cases such as polysensitization or idiopathic reactions, thus avoiding overuse of in vitro and in vivo IgE diagnostics. CRD may help the clinician to identify the cause of an allergy and, in the case of complex polysensitization, uncover possible cross-reactivity. Polysensitization, especially to inhalant allergens, is associated with the clinical appearance of asthma and allergic rhinitis; important risk factors for the latter are the major allergens Fel d 1 and Can f 1. Importantly, information on molecular sensitization patterns significantly influences the choice of specific immunotherapy and reduces its overprescription., Conclusion: At present, allergy diagnostics largely rely on clinical history, physical examination, and in vivo IgE testing. However, in vitro diagnostics including CRD are currently finding their way into the clinical routine and can offer additional information on the patient's sensitization profile and treatment responsiveness., (© 2018 American Association for Clinical Chemistry.)

Background: Grass pollen-related seasonal allergic rhinoconjunctivitis (SARg) is clinically heterogeneous in severity, comorbidities, and response to treatment. The component-resolved diagnostics disclosed also a high heterogeneity at molecular level. Our study aimed at analyzing the characteristics of the IgE sensitization to Phleum pratense molecules and investigating the diagnostic relevance of such molecules in childhood., Methods: We examined 1120 children (age 4-18 years) with SARg. Standardized questionnaires on atopy were acquired through informatics platform (AllergyCARD™). Skin prick tests were performed with pollen extracts. Serum IgE to airborne allergens and eight P. pratense molecules (rPhl p 1, rPhl p 2, rPhl p 4, rPhl p 5b, rPhl p 6, rPhl p 7, rPhl p 11, rPhl p 12) were tested by ImmunoCAP FEIA., Results: The analysis of IgE responses against eight P. pratense molecules showed 87 profiles. According to the number of molecules recognized by IgE, the more complex profiles were characterized by higher serum total IgE, higher grass-specific serum IgE, and higher number and degree of sensitization to pollens. The most frequent IgE sensitization profile was the monomolecular Phl p 1. Sensitization to Phl p 7 was a reliable biomarker of asthma, whereas Phl p 12 of oral allergy syndrome. Sensitization to Phl p 7 was associated with a higher severity of SARg, and complex profiles were associated with longer disease duration., Conclusions: In a large pediatric population, the complexity of IgE sensitization profiles against P. pratense molecules is related to high atopic features although useless for predicting the clinical severity. The detection of serum IgE to Phl p 1, Phl p 7, and Phl p 12 can be used as clinical biomarkers of SARg and comorbidities. Further studies in different areas are required to test the impact of different IgE molecular profiles on AIT response., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: In early childhood, the allergen-specific IgG repertoire is mainly directed to animal and vegetable food molecules and infrequently to airborne molecules. It is unknown whether this early pattern is maintained throughout childhood., Objective: To investigate the evolution of IgG and IgE responses to a broad panel of allergenic molecules from birth to age 10 years., Methods: We examined the sera collected between birth and age 10 years from participants in the German Multicentre Allergy Study, a birth cohort born in 1990. The IgE (cutoff ≥0.30 ISU) and IgG (cutoff ≥0.10 ISU) responses to 35 genuine allergenic molecules were measured with a multiplex microarray approach (ImmunoCAP ISAC™)., Results: IgE responses were mostly directed against a restricted group of airborne molecules, with a sequence and prevalence hierarchy (Phl p 1> Bet v 1> Fel d 1> Phl p 5> Der p 2> Der p 1) largely maintained over time. Conversely, the IgG repertoire was much broader, starting with animal foodborne, then spreading to vegetable foodborne and finally to airborne molecules. A strong and persistent IgG response to a given airborne molecule almost invariably preceded or accompanied an IgE response to that molecule., Conclusions: The evolution of IgG and IgE responses throughout childhood differs widely at population level. IgG responses are mostly directed to animal food allergens, while IgE responses are dominated by airborne allergens. However, a strong IgG response almost invariably precedes or accompanies the appearance of IgE to the same molecule in specifically sensitized subjects., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Pollen-food syndrome (PFS) is heterogeneous with regard to triggers, severity, natural history, comorbidities, and response to treatment. Our study aimed to classify different endotypes of PFS based on IgE sensitization to panallergens., Methods: We examined 1271 Italian children (age 4-18 years) with seasonal allergic rhinoconjunctivitis (SAR). Foods triggering PFS were acquired by questionnaire. Skin prick tests were performed with commercial pollen extracts. IgE to panallergens Phl p 12 (profilin), Bet v 1 (PR-10), and Pru p 3 (nsLTP) were tested by ImmunoCAP FEIA. An unsupervised hierarchical agglomerative clustering method was applied within PFS population., Results: PFS was observed in 300/1271 children (24%). Cluster analysis identified five PFS endotypes linked to panallergen IgE sensitization: (i) cosensitization to ≥2 panallergens ('multi-panallergen PFS'); (ii-iv) sensitization to either profilin, or nsLTP, or PR-10 ('mono-panallergen PFS'); (v) no sensitization to panallergens ('no-panallergen PFS'). These endotypes showed peculiar characteristics: (i) 'multi-panallergen PFS': severe disease with frequent allergic comorbidities and multiple offending foods; (ii) 'profilin PFS': oral allergy syndrome (OAS) triggered by Cucurbitaceae; (iii) 'LTP PFS': living in Southern Italy, OAS triggered by hazelnut and peanut; (iv) 'PR-10 PFS': OAS triggered by Rosaceae; and (v) 'no-panallergen PFS': mild disease and OAS triggered by kiwifruit., Conclusions: In a Mediterranean country characterized by multiple pollen exposures, PFS is a complex and frequent complication of childhood SAR, with five distinct endotypes marked by peculiar profiles of IgE sensitization to panallergens. Prospective studies in cohorts of patients with PFS are now required to test whether this novel classification may be useful for diagnostic and therapeutic purposes in the clinical practice., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The availability of allergen molecules ('components') from several protein families has advanced our understanding of immunoglobulin E (IgE)-mediated responses and enabled 'component-resolved diagnosis' (CRD). The European Academy of Allergy and Clinical Immunology (EAACI) Molecular Allergology User's Guide (MAUG) provides comprehensive information on important allergens and describes the diagnostic options using CRD. Part A of the EAACI MAUG introduces allergen molecules, families, composition of extracts, databases, and diagnostic IgE, skin, and basophil tests. Singleplex and multiplex IgE assays with components improve both sensitivity for low-abundance allergens and analytical specificity; IgE to individual allergens can yield information on clinical risks and distinguish cross-reactivity from true primary sensitization. Part B discusses the clinical and molecular aspects of IgE-mediated allergies to foods (including nuts, seeds, legumes, fruits, vegetables, cereal grains, milk, egg, meat, fish, and shellfish), inhalants (pollen, mold spores, mites, and animal dander), and Hymenoptera venom. Diagnostic algorithms and short case histories provide useful information for the clinical workup of allergic individuals targeted for CRD. Part C covers protein families containing ubiquitous, highly cross-reactive panallergens from plant (lipid transfer proteins, polcalcins, PR-10, profilins) and animal sources (lipocalins, parvalbumins, serum albumins, tropomyosins) and explains their diagnostic and clinical utility. Part D lists 100 important allergen molecules. In conclusion, IgE-mediated reactions and allergic diseases, including allergic rhinoconjunctivitis, asthma, food reactions, and insect sting reactions, are discussed from a novel molecular perspective. The EAACI MAUG documents the rapid progression of molecular allergology from basic research to its integration into clinical practice, a quantum leap in the management of allergic patients., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In the European Union (EU), allergens used for diagnostic tests (TAs) are defined as medicinal products and have to be registered by national authorities. The current situation is not homogeneous. Existing authorizations need to be kept in the market in some EU states, while others need complete new authorizations requiring clinical trials, quality assurance methods, stability studies, and periodic safety update reports. Allergen manufacturers argue that offering a comprehensive panel of TAs may be economically disastrous. Expenses for initiation and maintenance of TA authorizations far exceed their related revenues and manufacturers may be forced to significantly limit their allergen portfolios. The availability of a wide range of high-quality TAs is very important for in vivo diagnoses of IgE-mediated allergies. Increased regulatory demands induce costs that need to be covered by public health organizations or reimbursed by health insurance companies., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose of Review: The aim of this review is to update readers on the growing impact of a molecular approach (CRD) to the diagnosis and treatment of children with respiratory allergies, Recent Findings: A large panel of highly purified natural or recombinant species-specific and cross-reacting allergenic molecules is now available for clinical purposes. Species-specific molecules allow identifying specific sensitization toward a given allergenic source. Cross-reacting molecules allow interpreting polysensitization patterns that cannot be detailed using routine skin prick tests or specific IgE tests based on allergenic extracts. These molecular tools are transforming and improving the interpretation of clinical and laboratory tests used to define patients' IgE-sensitization profile., Summary: The accurate dissection of the IgE repertoire offers new possibilities in the diagnosis, prophylaxis and treatment of pediatric allergic rhinoconjunctivitis and asthma.

Background: Allergic rhinoconjunctivitis and asthma evolve dynamically throughout childhood. Yet, data on the evolution of serum levels of IgE antibodies against airborne allergens throughout the first decade of life are scarce., Objective: To describe the patterns of new and persistent sensitization against airborne allergens including remission from birth to 10 years of age and the long-term clinical outcomes up to the age of 13 years., Methods: In 273 children from the Multi-Centre Allergy Study, a German birth cohort, IgE levels were determined against airborne allergens (Dermatophagoides pteronyssinus, cat and dog dander, birch and grass species pollens) at 2, 5, 7, and 10 years of age (ImmunoCAP, Phadia); allergic rhino-conjunctivitis and asthma were ascertained at the 13 years of age through a standardized questionnaire (International Study of Asthma and Allergies in Childhood)., Results: The prevalence of sensitization to each allergen increased steadily throughout childhood, and a hierarchy of sensitization prevalence (grass>birch>mites>cat>dog) was maintained from 5 years of age onwards. A mono-sensitization state was relatively short (measurable half-life=3 years) as additional sensitizations were acquired frequently, and relatively soon after the first one. Remission of weak sensitization (UNICAP classes 1-2) was also quite frequent, especially before 5 years of age. By contrast, stronger IgE responses (>3.5 kU/L) were invariably persistent. Early sensitization was associated with a higher tendency for poly-sensitization at 10 years of age and allergic rhino-conjunctivitis and/or asthma at 13 years of age., Conclusions: IgE responses against airborne allergens undergo dynamic changes throughout childhood, with a high frequency of new sensitization or remission. The long-term persistence and the clinical impact of IgE responses are affected by the intensity of IgE sensitization and the age of its onset.

Background: Oral food challenge (OFC) is the diagnostic 'gold standard' of food allergies but it is laborious and time consuming. Attempts to predict a positive OFC through specific IgE assays or conventional skin tests so far gave suboptimal results., Objective: To test whether skin test with titration curves predict with enough confidence the outcome of an oral food challenge., Methods: Children (n=47; mean age 6.2 +/- 4.2 years) with suspected and diagnosed allergic reactions to hen's egg (HE) were examined through clinical history, physical examination, oral food challenge, conventional and end-point titrated skin tests with HE white extract and determination of serum specific IgE against HE white. Predictive decision points for a positive outcome of food challenges were calculated through receiver operating characteristic (ROC) analysis for HE white using IgE concentration, weal size and end-point titration (EPT)., Results: OFC was positive (Sampson's score >or=3) in 20/47 children (42.5%). The area under the ROC curve obtained with the EPT method was significantly bigger than the one obtained by measuring IgE-specific antibodies (0.99 vs. 0.83, P<0.05) and weal size (0.99 vs. 0.88, P<0.05). The extract's dilution that successfully discriminated a positive from a negative OFC (sensitivity 95%, specificity 100%) was 1 : 256, corresponding to a concentration of 5.9 microg/mL of ovotransferrin, 22.2 microg/mL of ovalbumin, and 1.4 microg/mL of lysozyme., Conclusion: EPT is a promising approach to optimize the use of skin prick tests and to predict the outcome of OFC with HE in children. Further studies are needed to test whether this encouraging finding can be extended to other populations and food allergens.

Background: IgE sensitization to soy and wheat is classified as 'primary' when generated by food ingestion and 'secondary' when it as a consequence of primary sensitization to cross-reacting pollen antigens via inhalation. The age-specific relevance of these categories of sensitization throughout childhood is unknown., Objective: To monitor the natural course of IgE sensitization against common food allergens in childhood in relation to sensitization against cross-reactive airborne allergens., Methods: The German Multi-Centre Allergy Study with follow-up from birth to age 13 recruited initially 1314 children. IgE antibody levels against cow's milk, hen's egg, soy, wheat, mites, cat and dog dander, birch and grass pollens were tested. Longitudinal data were analysed from the 273 children with sera obtained at age 2, 5, 7 and 10 years of age., Results: The point prevalence of sensitization (>1.0 kU/L) to milk and egg allergens progressively decreased from about 4% at 2 years to <1% at 10 years. By contrast, the prevalence of IgE to wheat and soy progressively increased with age, from 2% to 7% (soy) and from 2% to 9% (wheat). At 10 years of age, IgE to grass pollen was detected in 97% and 98% of the children reacting against soy and wheat, respectively; IgE to birch pollen was observed in 86% and 82% of the children reacting against soy and wheat, respectively. Early IgE sensitization to soy or wheat preceded that to grass or birch pollen in only 4% and 8% of participants sensitized to soy and wheat, respectively., Conclusion: IgE sensitization to soy and wheat is relatively uncommon and mostly primary in early infancy, more frequent and mostly secondary to pollen sensitization at school age. Clinical Implications Awareness should be raised to avoid unnecessary diet restrictions due to the high frequency of clinically irrelevant, secondary sensitization to soy and wheat in schoolchildren with pollinosis.

Three hundred recruits were classified as either allergic or nonallergic to inhalant allergens on the basis of history, physical examination, skin testing, and RAST. Forty-nine (16.3%) were classified as allergic as they were affected by oculorhinitis and/or asthma. This diagnosis was compared with results obtained with PRIST and with a new commercially available multi-RAST test for inhalant allergy, Phadiatop (Pharmacia). Sixty subjects (20%), including all 49 allergic subjects, scored positive in the Phadiatop assay (100% sensitivity) while PRIST (cut-off 220 IU/mL) identified only 20/49 allergics (40.8% sensitivity). The correlation between RAST and Phadiatop was excellent. Phadiatop is much more sensitive than PRIST; furthermore, Phadiatop is easier, less expensive, and as reliable as RAST for use in mass screening programs.

Background Specific IgE to Staphylococcus aureus enterotoxins ( SE-IgE) has been associated with asthma. In the general population, we aimed to determine the prevalence of and risk factors for serum SE-IgE and to examine the association with asthma. Methods A postal questionnaire was sent to a random sample of adults in 19 centers across Europe. A random sample of respondents was invited for clinical examination upon which they answered a questionnaire, underwent skin prick tests ( SPTs) for common aeroallergens, and provided blood for measurement of total IgE and SE-IgE. Risks were analyzed within centers using weighted logistic regression, and overall estimates calculated using fixed-effects meta-analysis. Results 2908 subjects were included in this analysis. Prevalence of positive SE-IgE was 29.3%; no significant geographic variation was observed. In contrast to positive skin prick tests, SE-IgE was more common in smokers (<15 pack-year: OR 1.11, P = 0.079, ≥15 pack-year: OR 1.70, P < 0.001), and prevalence did not decrease in older age-groups or in those with many siblings. Total IgE concentrations were higher in those with positive SE-IgE than in those with positive SPT. SE-IgE was associated with asthma ( OR 2.10, 95% confidence interval [1.60-2.76], P = 0.001) in a concentration-dependent manner. This effect was independent of SPT result and homogeneous across all centers. Conclusions We report for the first time that SE-IgE is common in the general population throughout Europe and that its risk factors differ from those of IgE against aeroallergens. This is the first study to show that SE-IgE is significantly and independently associated with asthma in the general population. [ABSTRACT FROM AUTHOR]

Background: Stimulation of the immune system by gut microbes might prevent allergy development. Objective: The present study examined the hypothesis that sensitization to food allergens and atopic eczema are influenced by the infantile intestinal colonization pattern. Methods: Infants were recruited perinatally in Göteborg (n = 116), London (n = 108), and Rome (n = 100). Commensal bacteria were identified to the genus or species level in rectal (3 days) and quantitative stool cultures (7, 14, and 28 days and 2, 6, and 12 months of age). At 18 months of age, atopic eczema and total and food-specific IgE levels were assessed. These outcomes were modeled in relation to time to colonization with 11 bacterial groups and to ratios of strict anaerobic to facultative anaerobic bacteria and gram-positive to gram-negative bacteria at certain time points. Study center, mode of delivery, parity, and infant diet were included as covariates. Results: Neither atopic eczema nor food-specific IgE by 18 months of age were associated with time of acquisition of any particular bacterial group. Cesarean section delayed colonization by Escherichia coli and Bacteroides and Bifidobacterium species, giving way to, for example, Clostridium species. Lack of older siblings was associated with earlier colonization by Clostridium species and lower strict anaerobic/facultative anaerobic ratio at 12 months. Conclusions: This study does not support the hypothesis that sensitization to foods or atopic eczema in European infants in early life is associated with lack of any particular culturable intestinal commensal bacteria. Clinical implications: The nature of the microbial stimulus required for protection from allergy remains to be identified. [Copyright &y& Elsevier]

Background Infection with influenza virus has been associated with seemingly opposing effects on the development of asthma. However, there are no data about the effects of mucosal vaccination with inactivated influenza on the inception of allergic asthma. Objective To assess the immunological effects of inhaled inactivated influenza vaccine, using two different types of flu vaccines, on the inception of allergic sensitization and allergen-mediated airway disease in a mouse model. Methods BALB/c mice were intranasally or intratracheally vaccinated with whole or split influenza virus vaccine (days −1 or −1, 27) before systemic sensitization with ovalbumin (OVA) (days 1, 14) and repeated airway allergen challenges (days 28–30). Allergen sensitization (IgE serum levels), airway inflammation (differential cells in bronchoalveolar lavage fluid) and airway hyper-reactivity (AHR) ( in vivo lung function) were analysed. Results The intranasal instillation of whole influenza vaccine before allergen sensitization significantly reduced the serum levels of total and OVA-specific IgE as well as allergen-induced AHR. Prevention was due to an allergen-specific shift from a predominant T helper (Th)2- towards a Th1-immune response. Application of split influenza vaccine did not show the same preventive effect. Conclusion Intranasal administration of inactivated whole influenza vaccine reduced subsequent allergen sensitization and prevented allergen-induced AHR. Our results show that the composition of the influenza vaccine has a major influence on subsequent development of allergen-induced sensitization and AHR, and suggest that mucosal inactivated whole influenza vaccination may represent a step towards the development of a preventive strategy for atopic asthma. [ABSTRACT FROM AUTHOR]

Background: Studies of immigrants represent an useful tool to determine the relative relevance of environmental vs genetic factors in causing the reported rapid increase of the prevalence of sensitization and allergic diseases. Methods: A total of 152 Albanian migrants to Southern Italy responded to a questionnaire based on the European Community Respiratory Health Survey (ECRHS) and 139 of them underwent skin prick test, and 61 serological assays for total IgE and IgG antibodies against Toxoplasma gondii (TG), herpes simplex virus 1 (HSV-1), hepatitis A virus (HAV) and Helicobacter pylori (HP). Results: Reported asthma was rare (2/152; 1.3%) and reported nasal allergies rather frequent (24/152; 15.8%). Sensitization to common inhalant allergens occurred in 27/139 (19.4%) subjects. The frequency of skin sensitization to pollen ( P = 0.003) and that of hay fever ( P = 0.004) increased with the time spent in Apulia. All the 61 sera had antibodies against HAV, 59/61 (96.7%) against HSV-1, 48/61 (78.7%) against HP and 34/61 (55.7%) against TG. The prevalence of skin sensitization and hay fever symptoms were correlated to the duration of residence in Southern Italy. Conclusions: Data presented indicate that Albanian migrants to Italy, in spite of the low prevalence of allergic diseases and sensitization in their country of origin, manifest with time an increasing prevalence of sensitization to local allergens and nasal symptoms after immigration to Italy. This would suggest a permanent role of allergen exposure and lifestyle factors in influencing the appearance of sensitization and symptoms of allergic diseases. [ABSTRACT FROM AUTHOR]

The validity of Phadiatop® as a tool in the mass screening for inhalant allergies was investigated. Seventy-nine out of 600 recruits (13.2%) were classified as allergic to inhalant allergens (68 oculorhinitis; 11 asthma) on the basis of positive history, confirmed by skin testing and/or RAST for the seven most common aero-allergens in Italy. Another 74 subjects had positive RAST and/or skin tests, yet had never experienced allergic symptoms. Phadiatop was positive in 145/600: in 78 out of 79 allergies and in 67 RAST-positive non-allergies. Correlation between Phadiatop and RAST was statistically significant, though higher for grass pollens (r= 0.85. P < 0.001) than for Dermatophagoides pteronyssinus (r = 0.68. P < 0.01). PRIST (cut-off 220 1U/ml) identified 36/79 allergies (45.6%, sensitivity, whereas that of Phadiatop was 98.7%). As the high percentage of cases in the unselected population had specific serum IgE against inhalant allergens and no allergic symptomatology, the Phadiatop-positive predictive value falls to 53.7%, thus creating the need for Phadiatop-positive subjects to undergo further investigation for an appropriate diagnosis. Given this limitation, Phadiatop appears to be an important step forward in the field of mass-screening programmes for inhalant allergies. [ABSTRACT FROM AUTHOR]