• Rats
• Mice
• Animals
• Allergens/chemistry
• Allergens/genetics
• Escherichia coli/genetics
• Immunoglobulin E
• Rats, Wistar
• Recombinant Proteins
• Immunoglobulin G
• Amino Acids

• Allergen immunotherapy
• Allergic rhinitis
• Future
• Intralymphatic immunotherapy
• Recombinants
• Regulatory

• Child
• Adolescent
• Humans
• COVID-19 Vaccines
• Rhinitis, Allergic/therapy
• Desensitization, Immunologic
• Allergens/therapeutic use
• Forecasting

• Insect venom allergy
• Intradermal test
• Skin prick test
• Specific IgE
• Venom immunotherapy

The aim of the present study was to determine the pattern of symptoms of ragweed pollen-induced allergic disease in sensitized patients from Romania and to compare the molecular diagnosis of allergy with the skin prick test, in order to better characterize allergic patients and to guide therapy. A total of 97 subjects, including patients with ragweed pollen-induced allergic rhinoconjunctivitis with/without asthma, as well as healthy controls, were recruited prospectively in one ragweed pollen season, submitted to allergy questionnaires, skin prick tests and multiplex specific IgE (immunoglobulin E) measurement by ImmunoCAP ISAC (ImmunoCAP Immuno-Solid phase Allergy Chip) assay. A total of 83 patients were sensitized to ragweed pollen. Most patients (73%) were diagnosed with moderate-severe intermittent allergic rhinoconjunctivitis and 25% of the patients also had allergic asthma. The most common symptoms were watery rhinorrhea (91.57%), nasal obstruction (86.75%), and sneezing (85.54%). Most patients were polysensitized (62.65%), especially to other pollens, house dust mites and animal danders. Only 90% of the patients with positive skin prick test to ragweed pollen extract also had increased specific serum IgE to Amb a 1. Current options for specific molecular diagnosis of ragweed allergy are limited, as they only contain one or few of the sensitizing allergens present in ragweed pollen. An improved component-resolved diagnosis, using several ragweed pollen allergens, is required for better patient characterization and subsequent selection of an appropriate allergen immunotherapy product, thereby enabling a more personalized approach to the management of the ragweed-allergic patient.

• IgE
• ImmunoCAP ISAC assay
• allergic rhinoconjunctivitis
• molecular diagnosis
• ragweed pollen allergy
• skin prick test

En la evaluación del paciente con sospecha de alergia las pruebas de detección y cuantificación de la inmunoglobulina E (IgE) específica in vitro se usan de manera habitual en los laboratorios clínicos para ayudar en el diagnóstico de la alergia. Actualmente existen diferentes alternativas comerciales para realizar estos ensayos, pero los resultados obtenidos por cada uno de ellos pueden variar, lo que condiciona el diagnóstico y el tratamiento que se le proporcionará al paciente. Con el fin de dar respuesta a los retos planteados por las diferencias entre las distintas técnicas para la determinación in vitro de la IgE específica, un grupo de expertos ha recogido en un documento una serie de recomendaciones sobre las implicaciones que puede tener el uso de una determinada técnica in vitro y el impacto en el manejo del paciente alérgico que suponen las diferencias entre las distintas técnicas. La lectura y el análisis de este documento de consenso ayudarán a entender las implicaciones que tiene el cambio de método de diagnóstico in vitro en el manejo del paciente con alergia, en su calidad de vida y en los costes socioeconómicos asociados a la enfermedad.

• alergia
• diagnóstico in vitro
• inmunoglobulina e
• recomendaciones

• allergy
• diagnosis in vitro
• immunoglobulin E
• recommendations

• Children
• Cow's milk allergy
• Food allergy
• Oral food challenge
• Skin-prick test
• Specific immunoglobulin E

• IgE
• allergy diagnosis
• pollen
• rhinitis

The burden of asthma in Africa is high, and yet the disease is not universally prioritised. Data on allergic asthma and its impact on asthma morbidity are limited in Africa. Our aim was to describe the distribution of skin prick positivity among asthmatics in Eastern Africa.

From August 2016 to May 2018, 1671 asthmatic patients were enrolled from Uganda, Kenya, and Ethiopia as part of the African Severe Asthma Program clinical study. Skin prick testing was performed at baseline using a panel of 12 allergens, and factors associated with skin prick reactivity determined.

Of the 1, 671 patients recruited, 71% were female with a median age of 40 years, 93.6% were aged >15 years and the patterns of asthma symptom frequency was intermittent in 2.9%, mild persistent in 19.9%, moderate persistent in 42.6% and severe persistent in 34.6% at baseline. Self-reported triggers, were dust (92%), cold weather (89%), upper respiratory infections (84%), strong smells (79%) and exposure to tobacco (78%). The majority (90%) of the participants had at least 1 positive allergen reaction, with 0.9% participants reacting to all the 12 allergens. Participants commonly reacted to house dust mites (66%), Blomia tropicalis (62%), and the German cockroach (52%). Patients sensitized to more allergens (>2) had significantly reduced lung function (FEV ≤ 80%; p = 0.001) and were more likely to visit the emergency department due to asthma (p = 0.012). There was no significant relationship between number of allergens and measures of asthma control, quality of life, and other clinical outcomes. Only the country of origin was independently associated with atopy among African asthmatics.

There is a high prevalence of skin prick positivity among East African patients with asthma, with the commonest allergen being house dust mite. Skin reactivity did not correlate well with asthma severity and poor asthma control. The relation between atopy, measured through skin prick testing, and measures of asthma control among asthma patients in Eastern Africa is unclear and needs further study.

The ASAP study was registered prospectively. ClinicalTrials.gov Identifier: NCT03065920; Registration date: February 28, 2017; Last verified: February 28, 2017.

• A. fumigatus, Aspergillus fumigatus
• ACT, Asthma control test
• AQLQ, Asthma Quality of Life Questionnaire
• ASAP, African Severe Asthma Project
• Africa
• Allergy
• Asthma
• Atopy
• COPD, Chronic obstructive pulmonary disease
• East Africa
• FEV, Forced Expiratory Volume
• HIV, Human immunodeficiency virus
• IQR, Interquartile range
• Ig, Immunoglobulin
• SPT
• SPT, Skin prick testing
• TB, Tuberculosis

• Allergen
• IgE
• IgE tests
• allergen immunotherapy
• allergic rhinitis
• asthma
• biomarker
• component-resolved diagnostics
• diagnostic algorithm
• molecular allergology
• molecular spreading

Precision allergy molecular diagnostic applications (PAMD@) is increasingly entering routine care. Currently, more than 130 allergenic molecules from more than 50 allergy sources are commercially available for in vitro specific immunoglobulin E (sIgE) testing. Since the last publication of this consensus document, a great deal of new information has become available regarding this topic, with over 100 publications in the last year alone. It thus seems quite reasonable to publish an update. It is imperative that clinicians and immunologists specifically trained in allergology keep abreast of the new and rapidly evolving evidence available for PAMD@.

PAMD@ may initially appear complex to interpret; however, with increasing experience, the information gained provides relevant information for the allergist. This is especially true for food allergy, Hymenoptera allergy, and for the selection of allergen immunotherapy. Nevertheless, all sIgE tests, including PAMD@, should be evaluated within the framework of a patient's clinical history, because allergen sensitization does not necessarily imply clinical relevant allergies.

• Cross reactivity
• Diagnosis
• Molecular allergy
• Panallergen
• Specific IgE, PAMD@

• AAAAI, American Academy of Allergy Asthma and Immunology
• ABA, Allergen Bead Array
• ACAAI, American College of Allergy Asthma and Immunology
• AEC, Allergen Exposure Chambers
• AIT, allergen immunotherapy
• AP, Alkaline Phosphatase
• AU/mL, Allergenic Units milliLiter
• Allergy
• Anti-IgE, Antibody against IgE
• BAT, Basophil Activation Test
• BAU/mL, Biologic Allergenic Units milliLiter
• CBA, Cytometric Bead Array
• CCD, Cross-reactive Carbohydrate Determinants
• CDER, Center for Drug Evaluation and Research (USA)
• CL, Chemiluminescence
• CaFE, Calibrated Fluorescence Enhancement
• DBPCFC, Double-Blind Placebo-Controlled Food Challenge
• Diagnostic strategies
• EAACI, European Academy of Allergy and Immunology
• EIA, Enzyme Immune Assay
• ELISA, Enzyme Linked Immuno Sorbent Analysis
• EMEA, European MEdicine Agencies
• ENPP-3, EctoNucleotide Pyrophosphatase/Phosphodiesterase 3
• FACS, Fluorescence-Activated Cell Sorting
• FDA, Food and Drug Administration (U.S. Department of Health and Human Services)
• FEIA, Fluorescent Enzyme Immunoassays
• FcεRI, High affinity IgE receptor
• H1, Histamine 1 receptor
• H2, Histamine 2 receptor
• HPO, Horseradish Peroxidase
• IDT, Intradermal Test
• ISAC, Immuno-Solid phase Allergen Chip
• IUIS, International Union of Immunological Societies
• IVD, in vitro diagnostic tool
• IgE
• IgE, immunoglobulin E
• In vitro tests
• LAMP-3, Lysosomal-Associated Membrane Protein
• MBAD, Molecule Based Allergy Diagnostics
• MRGPRX2, Mas-related G protein receptor 2
• NIH, National Institutes of Health (USA)
• NMBAs, NeuroMuscular Blocking Agents
• NPA, Negative Percent Agreement
• NSAIDs, Non-Steroidal Anti-Inflammatory Drugs
• PPA, Positive Percent Agreement
• PPT, Prick-Prick Test
• RAST, Radio Allergo Sorbent Test
• SCAR, severe cutaneous adverse drug reactions
• SPT, Skin prick test
• Skin tests
• kUA/L, kilo Units of Allergen/Liter for allergen-specific IgE antibody assays
• mAb, Monoclonal Antibody
• pNPP, p-Nitrophenylphosphate
• sIgE, specific IgE
• w/v, weight /volume

Several compositions for determination of specific molecular components in allergens have recently been patented. The role of Molecular Allergy (MA) diagnostics in suspected IgE mediated allergic conditions is currently debated. Guideline reports have concluded that population-based studies involving evaluation of the usefulness of MA diagnostics are needed.

To evaluate the usefulness of MA diagnostics in a secondary pediatric referral center.

A total of 961 children and adolescents aged 0.2-18.8 (mean 7.0) years was included in a pro-spective observational survey. Inclusion criterion was a suspected diagnosis of an IgE mediated condition based on history and clinical symptoms and signs. If a specific diagnosis could not be reached from con-ventional investigations suspected peanut allergy, birch pollen allergy and associated cross-reactivity, insect allergy and triggering allergens for specific immunotherapy were assessed by MA diagnostics.

Based on conventional work-up a diagnostic conclusion was established in 946 patients (98.4%). MA diagnostics were performed in 15 individuals (1.6%), 7 girls and 8 boys aged 3.2 to 17.8 (mean 10.6) years. In 8 cases a specific diagnosis was established based on MA diagnostics; in 7 cases MA diagnostics could not improve diagnosis. MA were most frequently (N = 7 (14%)) used in children with peanut allergy (N = 50).

Most patients in a secondary pediatric referral center with suspected IgE mediated allergy can be managed by conventional diagnostic methods. MA diagnostics may be useful in small and selected subgroups as in patients with suspected peanut allergy, however, may not be helpful in all cases.

• Allergy
• asthma
• component resolved diagnosis
• eczema
• molecular allergy diagnostics
• peanut
• rhinitis
• urticaria.

• Allergy
• allergen
• component-resolved diagnostics
• laboratory testing
• sensitization
• specific immunoglobulin type E

• Allergy
• Anaphylaxis
• Exercise-induced anaphylaxis
• Food allergy
• Food-dependent exercise-induced anaphylaxis

• Adolescent
• Adult
• Anaphylaxis/diagnosis
• Anaphylaxis/pathology
• Exercise/physiology
• Female
• Food Hypersensitivity/diagnosis
• Food Hypersensitivity/pathology
• Humans
• Male
• Middle Aged
• Retrospective Studies
• Time Factors
• Young Adult

Molecular-based allergy diagnosis for the in vitro assessment of a patient immunoglobulin E (IgE) sensitization profile at the molecular level uses allergen molecules (also referred to as allergen components), which may be well-defined, highly purified, natural allergen components or recombinant allergens. Modern immunoassay methods used for the detection of specific IgE against aeroallergen components are either singleplex (such as the fluorescence enzyme immunoassay with capsulated cellulose polymer solid-phase coupled allergens, the enzyme-enhanced chemiluminescence immunoassay and the reversed enzyme allergosorbent test, with liquid-phase allergens), multiparameter (such as the line blot immunoassay for defined partial allergen diagnostics with allergen components coating membrane strips) or multiplex (such as the microarray-based immunoassay on immuno solid-phase allergen chip, and the two new multiplex nanotechnology-based immunoassays: the patient-friendly allergen nano-bead array, and the macroarray nanotechnology-based immunoassay used as a molecular allergy explorer). The precision medicine diagnostic work-up may be organized as an integrated “U-shape” approach, with a “top-down” approach (from symptoms to molecules) and a “bottom-up” approach (from molecules to clinical implications), as needed in selected patients. The comprehensive and accurate IgE sensitization molecular profiling, with identification of the relevant allergens, is indicated within the framework of a detailed patient’s clinical history to distinguish genuine IgE sensitization from sensitization due to cross-reactivity (especially in polysensitized patients), to assess unclear symptoms and unsatisfactory response to treatment, to reveal unexpected sensitizations, and to improve assessment of severity and risk aspects in some patients. Practical approaches, such as anamnesis molecular thinking, laboratory molecular thinking and postmolecular anamnesis, are sometimes applied. The component-resolved diagnosis of the specific IgE repertoire has a key impact on optimal decisions making for prophylactic and specific immunotherapeutic strategies tailored for the individual patient.

• Singleplex
• Multiplex
• Immunoglobulin E sensitization
• Aeroallergens
• Immunoassays

Background: Double-blind placebo-controlled food challenges (DBPCFCs) remain the gold standard for the diagnosis of food allergy; however, challenges require significant time and resources and place the patient at an increased risk for severe allergic adverse events. There have been continued efforts to identify alternative diagnostic methods to replace or minimize the need for oral food challenges (OFCs) in the diagnosis of food allergy.

Methods: Data was extracted for all IRB-approved, Stanford-initiated clinical protocols involving standardized screening OFCs to a cumulative dose of 500 mg protein to any of 11 food allergens in participants with elevated skin prick test (SPT) and/or specific IgE (sIgE) values to the challenged food across 7 sites. Baseline population characteristics, biomarkers, and challenge outcomes were analyzed to develop diagnostic criteria predictive of positive OFCs across multiple allergens in our multi-allergic cohorts.

Results: A total of 1247 OFCs completed by 427 participants were analyzed in this cohort. Eighty-five percent of all OFCs had positive challenges. A history of atopic dermatitis and multiple food allergies were significantly associated with a higher risk of positive OFCs. The majority of food-specific SPT, sIgE, and sIgE/total IgE (tIgE) thresholds calculated from cumulative tolerated dose (CTD)-dependent receiver operator curves (ROC) had high discrimination of OFC outcome (area under the curves > 0.75). Participants with values above the thresholds were more likely to have positive challenges.

Conclusions: This is the first study, to our knowledge, to not only adjust for tolerated allergen dose in predicting OFC outcome, but to also use this method to establish biomarker thresholds. The presented findings suggest that readily obtainable biomarker values and patient demographics may be of use in the prediction of OFC outcome and food allergy. In the subset of patients with SPT or sIgE values above the thresholds, values appear highly predictive of a positive OFC and true food allergy. While these values are relatively high, they may serve as an appropriate substitute for food challenges in clinical and research settings.

• AUC
• biomarker evaluation
• cumulative tolerated dose
• food challenge
• time-dependent ROC

Classical allergy diagnostic workup “from symptoms to molecules” comprises 1) clinical investigation, 2) skin prick- and IgE- testing, and recently, 3) molecular allergy testing. We aimed to examine the diagnostic fidelity of the alternative approach “from molecules to symptoms”, which was recently suggested in the EAACI Molecular Allergology User’s Guide, in a retrospective clinical study.

Records from 202 patients with clinically suspected allergic sensitizations were extracted from files at two sites applying either the “ISAC-first” workup with IgE-testing by immuno-solid phase allergen chip ISAC112 followed by selected skin prick tests (SPT) or the “SPT-first” starting with SPT followed by the microarray test.

In the ISAC-first procedure significantly less SPTs were performed during allergy diagnosis (median 4 vs. 14). By SPT in 19% of patients in the ISAC-first group and in 34% in the SPT-first group additional respiratory allergens (p = 0.014) were detected not positive in ISAC microarray. By ISAC microarray test 18% additional sensitizations were found in the ISAC-first, and 32% in SPT-first cohort (p = 0.016). For food allergens 13 and 12% additional sensitizations were detected by the microarray not detected by SPT in the two groups (p = 0.800). No additional food allergen was found by SPT in the ISAC-first group, while in 6% of the cases in the SPT-first group detected sensitizations were negative in the microarray.

The ISAC-first approach followed by (fewer) SPTs meets the demands for a patient’s tailored diagnostic work-up and therefore can be considered equivalent to the conventional way using the skin prick test as first screening tool, followed by IgE diagnosis.

For the diagnostic verification of clinically suspected allergy, the novel concept “from molecules to clinic” offers a reliable diagnostic workup in shorter time. Due to lower skin test numbers it is especially applicable for young children and seniors, in atopic patients, and whenever skin tests get difficult or unreliable.

The online version of this article (10.1186/s40413-018-0199-y) contains supplementary material, which is available to authorized users.

• Allergy diagnosis
• Component-resolved diagnosis
• ISAC microarray
• IgE
• Molecular allergens
• Skin prick test

Companion animals are also affected by IgE‐mediated allergies, but the eliciting molecules are largely unknown. We aimed at refining an allergen microarray to explore sensitization in horses and compare it to the human IgE reactivity profiles.

Custom‐designed allergen microarray was produced on the basis of the ImmunoCAP ISAC technology containing 131 allergens. Sera from 51 horses derived from Europe or Japan were tested for specific IgE reactivity. The included horse patients were diagnosed for eczema due to insect bite hypersensitivity, chronic coughing, recurrent airway obstruction and urticaria or were clinically asymptomatic.

Horses showed individual IgE‐binding patterns irrespective of their health status, indicating sensitization. In contrast to European and Japanese human sensitization patterns, frequently recognized allergens were Aln g 1 from alder and Cyn d 1 from Bermuda grass, likely due to specific respiratory exposure around paddocks and near the ground. The most prevalent allergen for 72.5% of the tested horses (37/51) was the 2S‐albumin Fag e 2 from buckwheat, which recently gained importance not only in human but also in horse diet.

In line with the One Health concept, covering human health, animal health and environmental health, allergen microarrays provide novel information on the allergen sensitization patterns of the companion animals around us, which may form a basis for allergen‐specific preventive and therapeutic concepts.

• ISAC
• IgE
• allergen
• component-resolved diagnosis
• horse
• microarray
• molecular

Food allergy is a public health problem that has increased in the last decade. Despite the increasing rates in children, quality data on the burden of these diseases is lacking particularly in developing countries. Honduras has no studies in pediatric patients.

The objective of this research was to identify the most common sensitization patterns to food through epicutaneous skin testing and food allergy rates in children and their correlation with common allergic diseases in a group of patients from Hospital of Pediatrics Maria.

Cross-sectional retrospective, descriptive study in which records and database of all allergic patients in the immunology outpatient clinic from Hospital of Pediatrics Maria were reviewed between the periods of January 2015 through June 2016.

A total of 365 children were analyzed, the age of participants were in the range from 1 to 18 years, with an average of 9.8 years. Sensitization to food allergens were found in 23, and 58.3% were poly-sensitized. The most common food allergens that patients were sensitized to: milk 9.0%, eggs 6.9%, peanut 4.9% and pork meat 4.4%. Food allergy was confirmed via oral food challenged in 9.3% of the patients. The most frequent food allergies found were: cow’s milk allergy 6%, hen’s egg allergy 5.2% and wheat allergy 1.9%.

Milk and egg were the most common a food allergens found in the population studied. Most of the patients were found to be poly-sensitized. The frequent food allergies confirmed via oral food challenge were cow’s milk allergy, hen’s egg allergy and wheat allergy.

• Allergens
• Allergy
• Children
• Sensitization
• Skin prick test

• Adolescent
• Adult
• Case-Control Studies
• Female
• Humans
• Male
• Middle Aged
• Norepinephrine/blood
• Oxytocin/blood
• Pilot Projects
• Poaceae/immunology
• Pollen/immunology
• Rhinitis, Allergic/blood
• Rhinitis, Allergic/diagnosis
• Rhinitis, Allergic/immunology
• Skin Tests
• Stress, Psychological/blood
• Stress, Psychological/immunology
• Young Adult

• Austrian Science Fund

The initial laboratory approach in the diagnosis of allergies is to detect the type of allergic reaction, i.e. whether the patient’s allergy is mediated by immunoglobulin E (IgE) or not. For this purpose, the concentration of total serum IgE (tIgE) and specific IgE (sIgE) are determined. Progress in laboratory diagnostics is the use of component-resolved diagnosis (CRD) which implies determination of sIgE against purified native and recombinant allergenic molecules. Component-resolved diagnosis is used in laboratory practice as singleplex and multiplex assays. The choice of allergen for singleplex assay is based on anamnesis, clinical findings of a patient and on skin prick test results. Multiplex-microarray assays simultaneously determine multiple sIgE’s against numerous allergens. The goal of CRD is to distinguish the true allergens from the cross-reactive allergen molecules. Component-resolved diagnosis allows predicting the risk of severe symptoms, as well as anticipating the development of allergies. Thus, determination of sIgE against allergenic components may significantly improve current diagnostics of allergy. Since this method is applied in laboratory practice just a few years, it is necessary to acquire new knowledge and experience, to establish good co-operation between specialist in medical biochemistry and laboratory medicine and the specialist allergologist, so that the method can be applied in a rational manner. Component-resolved diagnosis will significantly improve the diagnostics of IgE-mediated allergy in the future. The aim of this article is to present potentials of CRD in the laboratory diagnostics of allergy mediated by IgE.

• IgE
• allergy
• component-resolved diagnosis