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Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE-mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE-mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well-defined, highly pure molecules for component-resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the "EAACI Molecular Allergology User's Guide" (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state-of-the-art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure., (© 2023 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

One hundred and ten years after Noon's first clinical report of the subcutaneous application of allergen extracts, allergen immunotherapy (AIT) has evolved as the most important pillar of the treatment of allergic patients. It is the only disease-modifying treatment option available and the evidence for its clinical efficacy and safety is broad and undisputed. Throughout recent decades, more insights into the underlying mechanisms, in particular the modulation of innate and adaptive immune responses, have been described. AIT is acknowledged by worldwide regulatory authorities, and following the regulatory guidelines for product development, AIT products are subject to a rigorous evaluation before obtaining market authorization. Knowledge and practice are anchored in international guidelines, such as the recently published series of the European Academy of Allergy and Clinical Immunology (EAACI). Innovative approaches continue to be further developed with the focus on clinical improvement by, for example, the usage of adjuvants, peptides, recombinants, modification of allergens, new routes of administration, and the concomitant use of biologicals. In addition, real-life data provide complementary and valuable information on the effectiveness and tolerability of this treatment option in the clinical routine. New mobile health technologies and big-data approaches will improve daily treatment convenience, adherence, and efficacy of AIT. However, the current coronavirus disease 2019 (COVID-19) pandemic has also had some implications for the feasibility and practicability of AIT. Taken together, AIT as the only disease-modifying therapy in allergic diseases has been broadly investigated over the past 110 years laying the path for innovations and further improvement., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Progressive knowledge of allergenic structures resulted in a broad availability of allergenic molecules for diagnosis. Component-resolved diagnosis allowed a better understanding of patient sensitization patterns, facilitating allergen immunotherapy decisions. In parallel to the discovery of allergenic molecules, there was a progressive development of a regulation framework that affected both in vitro diagnostics and Allergen Immunotherapy products. With a progressive understanding of underlying mechanisms associated to Allergen immunotherapy and an increasing experience of application of molecular diagnosis in daily life, we focus in analyzing the evidences of the value provided by molecular allergology in daily clinical practice, with a focus on Allergen Immunotherapy decisions., (© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The basis of allergen immunotherapy (AIT) is the diagnosis of the eliciting allergen sources, which is a challenge, especially in the case of multiple sensitizations. Molecular allergy diagnostics can be of special help, since detection of "marker allergens", usually important major allergens, allows to distinguish between primary sensitization and cross-reactions. Thus, the indication and extract selection for AIT can be facilitated. While molecular diagnosis is particularly useful for double-sensitized hymenoptera venom and polysensitized pollen allergic patients, the benefit is probably lower in case of house dust mite allergy., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Since its discovery in 1967, IgE antibody detection in skin and blood has identified a state of allergic sensitization and served as a necessary but not sufficient risk factor that requires objective symptoms to make the definitive diagnosis of human allergic disease. More recently, quantitative IgE antibody levels in serum against allergenic extracts, molecules, and epitopes have pushed its application into more accurately identifying the specificity of the allergic response for targeting immunotherapy, predicting allergic symptom severity after allergen exposure, and attempting to distinguish tolerance from food allergy. This review examines new in vivo and in vitro developments in the design, performance, interference, and application of the methods used to identify allergic sensitization. The increasing accepted applications of molecular allergen and allergen epitope-based IgE antibody measurements, especially as applied to food allergy diagnosis and management, are highlighted as state-of-the-art advances. Despite these major advances in allergic sensitization documentation, their ultimate value requires integration by the clinician with the patient's history and pretest probability of disease., (Copyright © 2020. Published by Elsevier Inc.)

Pollen from various Fagales tree species prolongs the season and makes tree pollen allergy a major health problem. Despite involving the same causative allergens, allergy immunotherapy (AIT) treatment habits differ significantly across different geographical regions. Diagnosis and treatment with AIT in patients allergic to tree pollen were discussed by a group of German medical experts who give practical recommendations based on the available data. Regulatory perspective: According to current guidelines on allergen products, birch pollen are the representative allergen source of the birch homologous group including several Fagales trees based on sequence and structural similarity of their allergen proteins. Immunological perspective: A high level of IgE cross-reactivity towards allergens from the birch homologous group has been observed in basic research and clinical trials. Clinical perspective: Clinical trial data show that the efficacy of birch pollen AIT is not only related to birch pollen allergy but extends to pollen from other trees, especially alder, hazel and oak. In order to optimize diagnosis and treatment of tree pollen allergy, the experts recommend to focus diagnosis and respective treatment with AIT primarily to birch as the representative allergen of the Fagales tree homologous group, but further diagnostics may be needed for some patients to determine adequate treatment., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Allergen immunotherapy (AIT) is a safe, effective treatment for allergic rhinoconjunctivitis and allergic asthma. However, AIT's clinical effect is still contested-primarily due to heterogeneity in clinical trial designs, study populations, therapeutic formulations, and efficacy criteria. After discussing current concepts and unmet needs, an international panel of experts made several recommendations: (i) explore and validate definitions for (clinical) responders in AIT trials; (ii) use of well-documented, standardized provocation tests prior to inclusion of subjects with relevant diseases in AIT trials; (iii) monitoring neo-sensitizations and occurrence of new allergy in extended AIT trials, and exclusion of polyallergic participants; (iv) validation of allergen exposure chambers with regard to natural exposure; (v) in studies of seasonal allergies, focus on peak exposure but also consider organizing two parallel, geographically distinct but otherwise identical trials; (vi) discuss adaptive trial designs with the regulatory authorities; (vii) use e-health and m-health technologies to capture more information on individual exposure to allergens; (viii) initiate research on potential psychological, biochemical, immune, neural, and even genomic markers of the placebo response; (ix) identify trial designs and primary endpoints that will give children with allergies easier, faster access to AIT formulations; and (x) promote and apply standardized methods for reporting systemic and local adverse events. The latest technologies and trial designs may provide novel, ethical ways of reducing bias and heterogeneity in AIT clinical trials. There is scope for physicians, patient organizations, companies, and regulators to improve clinical trials in AIT and, ultimately, to provide patients with better treatments., (© 2018 The Authors. Allergy Published by John Wiley & Sons Ltd.)

The Future of the Allergists and Specific Immunotherapy (FASIT) workshop provides a regular platform for global experts from academia, allergy clinics, regulatory authorities and industry to review developments in the field of allergen immunotherapy (AIT). The most recent meeting, held in February 2017, had two main themes: advances in AIT and hot topics in AIT from the regulatory point of view. The first theme covered opportunities for personalized AIT, advances in adjuvants and delivery systems, and the development of new molecules and future vaccines for AIT. Key topics in the second part of the meeting were the effects of the enactment of European Directive 2001/83 on the availability of allergens for therapy and diagnosis across the EU, the challenges of conducting Phase 3 studies in the field, the future role of allergen exposure chambers in AIT studies and specific considerations in performing AIT studies in the paediatric population. Finally, the group highlighted the forthcoming EAACI guidelines and their particular importance for the standardization of practice in the treatment of allergies. This review presents a comprehensive insight into those panel discussions and highlights unmet needs and also possible solutions to them for the future., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Allergic diseases are common and frequently coexist. Allergen immunotherapy (AIT) is a disease-modifying treatment for IgE-mediated allergic disease with effects beyond cessation of AIT that may include important preventive effects. The European Academy of Allergy and Clinical Immunology (EAACI) has developed a clinical practice guideline to provide evidence-based recommendations for AIT for the prevention of (i) development of allergic comorbidities in those with established allergic diseases, (ii) development of first allergic condition, and (iii) allergic sensitization. This guideline has been developed using the Appraisal of Guidelines for Research & Evaluation (AGREE II) framework, which involved a multidisciplinary expert working group, a systematic review of the underpinning evidence, and external peer-review of draft recommendations. Our key recommendation is that a 3-year course of subcutaneous or sublingual AIT can be recommended for children and adolescents with moderate-to-severe allergic rhinitis (AR) triggered by grass/birch pollen allergy to prevent asthma for up to 2 years post-AIT in addition to its sustained effect on AR symptoms and medication. Some trial data even suggest a preventive effect on asthma symptoms and medication more than 2 years post-AIT. We need more evidence concerning AIT for prevention in individuals with AR triggered by house dust mites or other allergens and for the prevention of allergic sensitization, the first allergic disease, or for the prevention of allergic comorbidities in those with other allergic conditions. Evidence for the preventive potential of AIT as disease-modifying treatment exists but there is an urgent need for more high-quality clinical trials., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Guidelines on the treatment of asthma, allergic rhinitis (AR), and allergen immunotherapy (AIT) lack recommendations for house dust mite (HDM) allergy. An expert panel reviewed current guidelines in the light of new data to assess whether guidelines could be improved. Most guidelines and key position papers did not provide specific recommendations on treatment of allergic asthma (AA) caused by HDM allergy, although some included AIT as a treatment option for AA in general. Around half of the guidelines stated that AIT with HDM extract was an effective treatment for AR, with several indicating sublingual immunotherapy as an option. This heterogeneity is caused by quality issues affecting studies of AIT with perennial allergens in patients with AA and AR, including use of different diagnosis and severity criteria, lack of consistent scoring or grading systems for primary and safety outcomes, and lack of consensus on treatment parameters. There is a need for well-designed clinical trials to serve as a basis for guideline recommendations. Although results from recent studies strengthen the evidence base for the efficacy and safety of sublingual immunotherapy in patients with HDM-induced AA and AR, their effect on subsequent guideline updates will depend on the methodology and evidence model used by each guideline., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: After the re-introduction of ImmunoCAP® ISAC sIgE 112 on the market, we undertook a study to evaluate the performance of this multiplex-based immunoassay for IgE measurements to allergen components., Methods: The study was carried out at 22 European and one South African site. Microarrays from different batches, eight specific IgE (sIgE) positive, three sIgE negative serum samples and a calibration sample were sent to participating laboratories where assays were performed according to the manufacturer's instructions., Results: For both the negative and positive samples results were consistent between sites, with a very low frequency of false positive results (0.014%). A similar pattern of results for each of the samples was observed across the 23 sites. Homogeneity analysis of all measurements for each sample were well clustered, indicating good reproducibility; unsupervised hierarchical clustering and classification via random forests, showed clustering of identical samples independent of the assay site. Analysis of raw continuous data confirmed the good accuracy across the study sites; averaged standardized, site-specific ISU-E values fell close to the center of the distribution of measurements from all sites. After outlier filtering, variability across the whole study was estimated at 25.5%, with values of 22%, 27.1% and 22.4% for the 'Low', 'Moderate to High' and 'Very High' concentration categories, respectively., Conclusions: The study shows a robust performance of the ImmunoCAP® ISAC 112 immunoassay at different sites. Essentially the same results were obtained irrespective of assay site, laboratory-specific conditions and instruments, operator, or the use of microarrays from different batches.

Background: There is a need to establish the effectiveness, cost-effectiveness, and safety of allergen immunotherapy (AIT) for the prevention of allergic disease., Methods: Two reviewers independently screened nine international biomedical databases. Studies were quantitatively synthesized using random-effects meta-analyses., Results: A total of 32 studies satisfied the inclusion criteria. Overall, meta-analysis found no conclusive evidence that AIT reduced the risk of developing a first allergic disease over the short term (RR = 0.30; 95% CI: 0.04-2.09) and no randomized controlled evidence was found in relation to its longer-term effects for this outcome. There was, however, a reduction in the short-term risk of those with allergic rhinitis developing asthma (RR = 0.40; 95% CI: 0.30-0.54), with this finding being robust to a pre-specified sensitivity analysis. We found inconclusive evidence that this benefit was maintained over the longer term: RR = 0.62; 95% CI: 0.31-1.23. There was evidence that the risk of new sensitization was reduced over the short term, but this was not confirmed in the sensitivity analysis: RR = 0.72; 95% CI: 0.24-2.18. There was no clear evidence of any longer-term reduction in the risk of sensitization: RR = 0.47; 95% CI: 0.08-2.77. AIT appeared to have an acceptable side effect profile., Conclusions: AIT did not result in a statistically significant reduction in the risk of developing a first allergic disease. There was, however, evidence of a reduced short-term risk of developing asthma in those with allergic rhinitis, but it is unclear whether this benefit was maintained over the longer term. We are unable to comment on the cost-effectiveness of AIT., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Prevention of Allergic Disease. We seek to critically assess the effectiveness, cost-effectiveness, and safety of AIT in the prevention of allergic disease., Methods: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesized., Discussion: The findings from this review will be used to inform the development of recommendations for EAACI's Guidelines on AIT., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Symptoms are recorded by obtaining a clinical history. Allergen sensitization is demonstrated by skin prick test or allergen-specific IgE serology. IgE sensitizations to allergen sources can be identified knowing the relationship between major aeroallergens and homologous allergen families. Some develop allergic sensitization to pan-allergens. Allergen extracts do not allow definitive separation of the sources. IgE antibody analysis of the major allergenic molecules facilitates differentiation of sensitizing allergen sources. IgE sensitizations to inhalant allergens are only relevant in the case of corresponding symptoms. In questionable cases, conjunctival or nasal provocation tests help induce confirmatory symptoms and identify relevant allergens for immunotherapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This article continues the comprehensive international consensus (ICON) statement on allergen immunotherapy (AIT). The initial article also recently appeared in the Journal. The conclusions below focus on key mechanisms of AIT-triggered tolerance, requirements in allergen standardization, AIT cost-effectiveness, and regulatory guidance. Potential barriers to and facilitators of the use of AIT are described in addition to future directions. International allergy specialists representing the European Academy of Allergy and Clinical Immunology; the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma and Immunology; and the World Allergy Organization critically reviewed the existing literature and prepared this summary of recommendations for best AIT practice. The authors contributed equally and reached consensus on the statements presented herein., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Although house dust mite (HDM) allergy is a major cause of respiratory allergic disease, specific diagnosis and effective treatment both present unresolved challenges. Guidelines for the treatment of allergic rhinitis and asthma are well supported in the literature, but specific evidence on the efficacy of pharmacotherapy treatment for known HDM-allergic patients is weaker. The standard diagnostic techniques--skin prick test and specific IgE testing--can be confounded by cross-reactivity. However, component-resolved diagnosis using purified and recombinant allergens can improve the accuracy of specific IgE testing, but availability is limited. Treatment options for HDM allergy are limited and include HDM avoidance, which is widely recommended as a strategy, although evidence for its efficacy is variable. Clinical efficacy of pharmacotherapy is well documented; however, symptom relief does not extend beyond the end of treatment. Finally, allergen immunotherapy has a poor but improving evidence base (notably on sublingual tablets) and its benefits last after treatment ends. This review identifies needs for deeper physician knowledge on the extent and impact of HDM allergy in respiratory disease, as well as further development and improved access to molecular allergy diagnosis. Furthermore, there is a need for the development of better-designed clinical trials to explore the utility of allergen-specific approaches, and uptake of data into guidance for physicians on more effective diagnosis and therapy of HDM respiratory allergy in practice., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Application of purified native and recombinant allergenic molecules into IgE antibody assays can improve analytical sensitivity and specificity for selected allergen specificities. They enhance analytical sensitivity by allowing assays to detect IgE antibodies with a lower limit of quantification (LoQ) to missing or poorly represented allergens in diagnostic extracts that are commonly used in vivo and in vitro. Use of selected allergenic molecules can help improve the clinician's prediction of the risk of a serious allergic reaction to stable allergens. They can provide diagnostic information to determine if a provocation challenge (e.g., oral food challenge) is indeed mandatory or not necessarily needed to support the final diagnostic decision. Suspected cross-reactivity based on the clinical history can be adjudicated by analyzing IgE antibodies to allergenic molecules from cross-reactive protein families. Finally, genuine primary sensitization can be identified by IgE antibody responses that are measured to selected allergenic molecules which are present in only one particular allergen source. After allergen-specific IgE detection, careful interpretation is required by the physician who knows the patient's history. Applying single allergen molecules, positive IgE antibody results are still only relevant in the case of corresponding objective symptoms. Subsequently, clinical relevance of such an IgE antibody test result must be determined by the clinician and not by the test itself. Because of their comprehensive nature, allergen extracts will remain the principal allergen source for diagnostic in vivo and in vitro assays of IgE antibody for many years. Judicious use of individual allergenic molecules in serum IgE assays may provide their most cost effective and efficient application for establishing a definitive diagnosis of human allergic disease.

The prevalence of allergy to furry animals has been increasing, and allergy to cats, dogs, or both is considered a major risk factor for the development of asthma and rhinitis. An important step forward in the diagnosis of allergy to furry animals has been made with the introduction of molecular-based allergy diagnostics. A workshop on furry animals was convened to provide an up-to-date assessment of our understanding of (1) the exposure and immune response to the major mammalian allergens, (2) the relationship of these responses (particularly those to specific proteins or components) to symptoms, and (3) the relevance of these specific antibody responses to current or future investigation of patients presenting with allergic diseases. In this review research results discussed at the workshop are presented, including the effect of concomitant exposures from other allergens or microorganisms, the significance of the community prevalence of furry animals, molecular-based allergy diagnostics, and a detailed discussion of cat and dog components., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Allergen-specific immunotherapy (SIT, desensitization) is applied monthly with subcutaneous injections (SCIT) or sublingually (SLIT) with droplets or tablets on a daily basis. Numerous immunological changes during SIT induce long-lasting tolerance. Efficacy has been demonstrated by a number of controlled studies for insect venom hypersensitivity (SCIT), allergic rhinoconjunctivitis (SCIT, SLIT particularly in grass pollen allergy), and allergic asthma (SCIT > SLIT). SIT is indicated in children and adults with severe allergic reactions from insect venoms (e.g., bee, wasp) or cumbersome symptoms from pollen, house dust mites or mold allergens and proven immediated-type allergy. Contraindications must be considered individually. SIT is performed for 3 years, in case of venom allergy 3-5 years. Severe systemic reactions are rare after SCIT. After SLIT rather local allergic symptoms of short duration occur in the mouth and throat. At present, the number prescriptions for SIT has decreased due to inadequate reimbursement of allergy-related services (diagnostics, therapies, monitoring). In the future, inferior medical care of allergic patients in Germany is expected, who until now have benefited from the preventive effects of SIT (reduced risk of developing asthma and new allergic sensitizations).

Background: For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen products for SIT are being increasingly required to conform to regulatory requirements for human medicines, which include the need to demonstrate dose-dependent effects., Methods: This report, produced by a Task Force of the EAACI Immunotherapy Interest Group, evaluates the currently available data on dose-response relationships in SIT and aims to provide recommendations for the design of future studies., Results: Fifteen dose-ranging studies fulfilled the inclusion criteria and twelve reported a dose-response relationship for clinical efficacy. Several studies also reported a dose-response relationship for immunological and safety endpoints. Due to the use of different reference materials and methodologies for the determination of allergen content, variations in study design, and choice of endpoints, no comparisons could be made between studies and, as a consequence, no general dosing recommendations can be made., Conclusion: Despite recently introduced guidelines on the standardization of allergen preparations and study design, the Task Force identified a need for universally accepted standards for the measurement of allergen content in SIT preparations, dosing protocols, and selection of clinical endpoints to enable dose-response effects to be compared across studies., (© 2011 John Wiley & Sons A/S.)

Background: Allergic sensitization to cat allergens is common and represents a major risk factor for asthma. Specific immunotherapy (SIT) is effective but cumbersome and associated with IgE-dependent adverse events. Immunotherapy targeting allergen-specific T cells, with synthetic peptides representing T-cell epitopes, might improve safety and reduce the duration of treatment., Objective: We sought to define major T-cell epitopes of Fel d 1 for peptide immunotherapy, generate a peptide vaccine, and evaluate its safety and tolerability in subjects with cat allergy., Methods: We determined the binding affinities of Fel d 1 peptides for 10 commonly expressed HLA-DR molecules. Functionally immunodominant peptides were identified by means of proliferation and cytokine secretion. Histamine-releasing activity was assessed, and a peptide vaccine was formulated. Safety and tolerability were evaluated in a dose-ranging phase IIa clinical trial., Results: MHC-binding sequences were identified throughout Fel d 1. Some regions contained multiple overlapping T-cell epitopes that bound multiple MHC molecules. Immunodominant sequences were identified on the basis of proliferative and cytokine (IFN-γ, IL-10, and IL-13) responses. Cat allergen extract, but not peptides, induced histamine release in blood basophils. A single administration of peptide vaccine was safe and well tolerated. The dose of vaccine resulting in the greatest inhibition of the late-phase skin response to intradermal whole allergen challenge was 3 nmol., Conclusions: Fel d 1 contains multiple overlapping MHC-binding motifs. A peptide vaccine comprising the immunodominant regions of the allergen was safe and well tolerated when given to subjects with cat allergy as a single dose. The dose of vaccine resulting in the greatest reduction in late-phase skin response was defined for future clinical development., (Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Inappropriate test methods are increasingly utilized to diagnose allergy. They fall into two categories: I. Tests with obscure theoretical basis, missing validity and lacking reproducibility, such as bioresonance, electroacupuncture, applied kinesiology and the ALCAT-test. These methods lack both the technical and clinical validation needed to justify their use. II. Tests with real data, but misleading interpretation: Detection of IgG or IgG4-antibodies or lymphocyte proliferation tests to foods do not allow to separate healthy from diseased subjects, neither in case of food intolerance, allergy or other diagnoses. The absence of diagnostic specificity induces many false positive findings in healthy subjects. As a result unjustified diets might limit quality of life and lead to malnutrition. Proliferation of lymphocytes in response to foods can show elevated rates in patients with allergies. These values do not allow individual diagnosis of hypersensitivity due to their broad variation. Successful internet marketing, infiltration of academic programs and superficial reporting by the media promote the popularity of unqualified diagnostic tests; also in allergy. Therefore, critical observation and quick analysis of and clear comments to unqualified methods by the scientific medical societies are more important than ever.

Background: Specific immunotherapy is the only causal treatment of allergy available today. Traditionally, therapeutic products based on either a single grass species or a mix of such extracts are used for grass pollen immunotherapy. Investigations comparing the immunological response to these allergen preparations are needed to ensure optimal treatment. The objective of this study was to investigate patterns of T and B cell cross-reactivity to Pooideae single-species extracts and to extract mixes., Methods: IgG4 induced by immunotherapy with Phleum pratense extract was investigated for cross-reactivity using nine single-species extracts and four mixes. For the mixes, studies of IgE cross-reactivity were also performed. T cell cross-reactivity was investigated in lines specific to nPhl p 1 or nPhl p 5 allergens, and the amounts of group 1 and 5 allergens in the extracts were quantified by a single radial immunodiffusion., Results: The levels of treatment-induced IgG4 detected by all the extracts displayed a clear correlation to that detected by the P. pratense pollen extract. The IgE studies confirmed the cross-reactivity of P. pratense-specific B cells towards the allergens contained in the mixes, and the T cell studies demonstrated cross-reactivity towards group 1 and 5 major allergens in extracts of six temperate grass species., Conclusion: Extensive T and B cell cross-reactivity was observed towards the allergens of the Pooideae grasses, and the degree of B cell cross-reactivity was independent of the number of species included in the extract mixes. This implies that treatment with pollen extract of just one Pooideae species will affect the allergic responses caused by any of the temperate grasses in this subfamily.

Allergen specific immunotherapy (SIT) is the only potentially curative treatment of IgE mediated allergic diseases. To ensure its effective use, many requirements must be met before and during therapy. Before starting immunotherapy, informed consent should be obtained, along with the consideration of the indications and contraindications. SIT should be prescribed and administered only by physicians with experience in allergic disease who are qualified to manage severe anaphylactic reactions. The clinical symptoms and the age of the patients determine the route of application, choice of allergen extracts and the duration of treatment. Numerous products and protocols facilitate an individualised therapy.

Background and Objective: The ELItest is a newly developed system to measure specific IgE based on allergen bound to paper rings and an alkaline phosphatase conjugated second antibody detection system. It was compared to the CAP system, a method based on allergen conjugated to an encapsulated cellulose polymer and a beta-galactosidase conjugated fluorescence detection system., Methods: Sera of 300 patients with positive history and positive skin-prick tests to common allergens (birch, timothy-grass, cat dander, dermatophagoides ptronyssinus, wasp venom) and 30 negative controls were tested in both systems. Serial dilutions of high titre sera were measured; inter- and intraassay coefficients of variation (cv) were determined., Results: The CAP system proved to be more sensitive (92.3%) compared to ELItest (84%) but marginally less specific (94.7% for CAP versus 96.7% for ELItest). Intraassay cv were slightly lower in the ELItest (7.2% CAP versus 6.4% ELItest), whereas the interassay cv was roughly twice as high for ELItest (20.1%) than for the CAP system (11.4%). Linearity over an 8-fold dilution was good in both tests (r2 0.979 ELItest versus 0.996 CAP), although ELItest levelled off at higher allergen concentrations. Similarly, correlation analysis between both systems revealed that ELItest consistently measured lower values, especially at higher concentrations of specific IgE. The slope of the linear regression line of a log/log plot of measured IgE concentrations was significantly lower than 1 in birch, cat and wasp; the y-intersect was significantly lower than 0 in all analysed allergens., Conclusion: These results suggest that the ELItest system for the measurement of specific IgE is not quite as reproducible and sensitive as the CAP system but slightly more specific, and that higher concentrations of specific IgE are measured lower in the ELItest. One potential reason might be that the amount of allergen bound to a paper ring might be smaller than that bound to a cellulose polymer, but further experiments are necessary to prove this hypothesis.

Histamine release (HR) studies were performed in 40 birch pollen-allergic patients (positive case history, positive SPT, positive birch pollen-specific serum IgE: RAST > or = 3) with (n = 20, A) and without (n = 20, B) fruit hypersensitivity, and 10 nonatopic volunteers (C). Several fruit allergens were used and characterized by protein determination and immunoblot techniques. Dose-dependent HR (apple peel = apple pulp > peach = cherry) was demonstrated in both allergic groups, but to a higher extent in patients with fruit allergy (P < 0.01). Increased basophil sensitivity to birch pollen was found in the group with fruit allergy (P < 0.001). Strong correlations between the mediator response induced by several fruits indicate common allergens within the extracts. We conclude that fruit-related symptoms require not only high specific serum IgE, but a strong cellular sensitization to birch pollen allergens together with an increased cellular reactivity to fruit allergens.

It was shown in two different provocation models (nasal and bronchial provocation) that substance P (SP) may play an important role in the neurogenic inflammatory response in upper and lower airway disease. (1) Pretreatment with SP augments the antigen challenge response of the nasal mucosa. (2) The baseline bronchoalveolar lavage (BAL) concentrations of SP are elevated 8-fold in allergies (pollen asthma) as compared with normals, even outside of season. (3) The SP concentration in BAL increases significantly (p less than 0.05) after bronchial allergen provocation. These findings support a previous hypothesis of an abnormally elevated activity of nonadrenergic-noncholinergic excitatory nerves and are in accordance with the results of a decreased activity of neutral endopeptidase exaggerating neurogenic inflammatory responses in the airways, including bronchomotor tone hyperresponsiveness.