Allergen Immunotherapy In Patients Research Articles

Latex immunotherapy: evidence of effectiveness.

IntroductionThe only etiological and decisive therapy, able to influence the natural history of latex allergy is the specific desensitization.AimTo verify the clinical efficacy and immunological changes determined by latex sublingual immunotherapy in allergic patients who underwent this treatment for at least 3 years.Material and methodsWe enrolled 76 patients (16 males and 60 females, mean age 34 years old) with evidence of a natural rubber latex allergy. To assess the effectiveness of the immunotherapy we performed a latex skin prick test, specific IgE and IgG4 and challenge tests before and after at least 3 years of desensitization.ResultsWe observed a reduction in the mean diameter of the wheal area at the skin prick test and a decrease in latex specific IgE while no significant changes of latex IgG4 values were found. Moreover a reduction of symptoms and scores at the provocation tests were remarked.ConclusionsAlthough the primary prevention (which still remains the gold standard treatment for patients suffering from the latex allergy) sublingual immunotherapy can be offered with efficacy in addition to symptomatic treatment to selected patients.

New Suggestions in Sublingual Immunotherapy for House Dust Mite- Related Allergic Diseases.

The indications for Allergen immunotherapy (AIT) in patients suffering from House Dust Mite (HDM)-related allergic diseases are presently based on incomplete data. This is essentially based on the fact that HDM allergy is difficult to evaluate in clinical trials, due to the largely variable allergen exposure and symptoms, and to the long periods of observation needed to assess the effects. In addition, at variance with pollen allergy, in HDM allergy asthma is more prevalent. However, several AIT products have been approved for HDM-induced allergic rhinitis, according to their ascertained clinical efficacy, tolerability and safety profile, particularly in the sublingual form (SLIT). We reviewed herein the available data on AIT in patients with HDM-induced allergic diseases, with a particular attention to the new product MK-8237 HDM-SLIT tablets, concerning its efficacy and safety profile. In the recent years, several randomized placebo-controlled clinical trials have been performed in Europe, North America and Japan to evaluate the efficacy of HDM-sublingual tablets in patients with HDM-induced allergic asthma and allergic rhinitis, mainly assessing the reduction of symptoms, exacerbations and corticosteroid intake. The results of the published clinical trials were encouraging and led to the approval and commercialization of MK-8237 HDM-SLIT tablet. The favorable efficacy and safety profile of MK-8237 HDM-SLIT tablets provided a consolidated therapeutic option for patients with HDM-induced allergic rhinitis and asthma.

Specific immunoglobulin E and immunoglobulin G4 toward major allergens of house-dust mite during allergen-specific immunotherapy.

Specific immunoglobulin E (sIgE) and sIgG4 to house-dust mite (HDM) major allergens during allergen immunotherapy (AIT) and their clinical relevance remain unclear. To investigate the variation of sIgE and sIgG4 to HDM major allergens and the correlation with clinical responses during AIT in patients with allergic rhinitis. Thirty-nine patients with HDM allergy were divided into the AIT group (taking immunotherapy) and the control group (medication only use). The AIT group was subdivided into negative clinical responses to AIT (nAIT) group and positive clinical responses to AIT (pAIT) group according to symptom relief and subjective evaluation. sIgE and sIgG4 to Dermatophagoides pteronyssinus (Dp) and Dermatophagoides farinae (Df), and their group 1 and group 2 major allergens (Dp1, Df1, Dp2, and Df2) were measured before AIT, at 6 months, and at 1 year after starting AIT. Dp2, Df, and Df2 sIgE values decreased significantly in the pAIT group versus the nAIT group after 1 year of AIT (median values of delta change were Dp2, -10.09 versus 5.89 kU/L, p = 0.001; median values of Df were -9.69 versus 17.54 kU/L, p = 0.004; median values of Df2 were -11.06 versus 20.08 kU/L, p = 0.013). There was a robust increase in the sIgG4 values to Dp, Df, and their major allergens in both the pAIT and the nAIT groups overall after 1 year of treatment. Patients with a positive response to AIT showed a significant reduction of HDM group 2 sIgEs compared with those with a negative response to AIT, which indicated that a decrease in group 2 sIgEs could be a marker that reflected AIT clinical efficacy.

Human Immune Monitoring Techniques during Food Allergen Immunotherapy.

Encouraging results from recent food allergen immunotherapy clinical trials indicate that the immune system plays an essential role in peripheral tolerance to food allergen. Thus, the monitoring of changes in immune responses and their possible correlation with clinical outcome in allergic patients receiving immunotherapies could theoretically serve as surrogate markers and be harnessed as rationale for food allergen immunotherapy development. A shift towards antigen specificity in recent assays has provided a solid foundation for the elucidation of cellular mechanisms involved in food allergen immunotherapy as well as the tracking of allergen-specific immune cells. In this review, we overview the current challenges and technologies used in immune monitoring during immunotherapy in allergic patients with a focus on cell-mediated immunity. We also discuss critical steps involved in some of the cellular immune assays utilized in clinical trials.

Anti-Interleukin-9 Antibody Increases the Effect of Allergen-Specific Immunotherapy in Murine Allergic Rhinitis.

PurposeInterleukin (IL)-9 induces allergic responses; however, the roles of anti-IL-9 antibody in the induction of tolerance remain unclear. This study investigated the effects of anti-IL-9 antibody on oral tolerance (OT) in a mouse model of allergic rhinitis (AR).MethodsBALB/c mice were divided into 4 groups: the control, AR, OT, and OT with anti-IL-9 antibody (OT+IL9AB) groups. Ovalbumin (OVA) was used for sensitization and challenge. Mice in the OT and OT+IL9AB groups were fed OVA for immunotherapy. During immunotherapy, OT+IL9AB mice were injected with anti-IL-9 antibody. Allergic symptoms, tissue eosinophil counts, and serum OVA-specific immunoglobulin E (IgE) were measured. The mRNA expressions of cytokines and transcription factors of T cells of nasal mucosa were determined by real-time polymerase chain reaction (PCR). The protein levels of GATA3, ROR-γt, and Foxp3 in nasal mucosa were determined by Western blot. CD4+CD25+Foxp3+ T cells in the spleen were analyzed by flow cytometry.ResultsAdministration of anti-IL-9 antibody decreased allergic symptoms, OVA-specific IgE levels, and eosinophil counts. In addition, it inhibited T-helper (Th) 2 responses, but had no effect on Th1 responses. Protein levels of ROR-γt and mRNA levels of PU.1 and ROR-γt were reduced by anti-IL-9 antibody. Anti-IL-9 antibody increased Foxp3 and IL-10 mRNA expression, Foxp3 protein, and induction of CD4+CD25+Foxp3+ T cells.ConclusionsAnti-IL-9 antibody decreased allergic inflammation through suppression of Th2 and Th17 cells. Anti-IL-9 antibody enhanced the tolerogenic effects of regulatory T cells. These results suggest that anti-IL-9 antibody might represent a potential therapeutic agent for allergen immunotherapy in patients with uncontrolled allergic airway disease.

Clinical Efficacy of Subcutaneous Allergen Immunotherapy in Patients with Atopic Dermatitis

PurposeThe clinical usefulness of subcutaneous allergen immunotherapy (SCIT) in the treatment of atopic dermatitis (AD) is still controversial. We analyzed the clinical efficacy of SCIT in patients with AD and the clinical characteristics of patients showing a favorable clinical response to the treatment.Materials and MethodsTwo hundred and fifty one patients with AD sensitized to house dust mite (HDM) were treated by SCIT using HDM extract. The clinical severity of AD was measured using the standardized clinical severity scoring system for AD (SCORAD) at baseline and 12 months. A favorable clinical response to SCIT was defined as a decrease in SCORAD value at 12 months greater than 50% compared to baseline value. Severe AD was defined as a baseline SCORAD value above 50.ResultsA favorable clinical response to SCIT was observed in 73.6% of patients. The proportion of patients showing a favorable clinical response to SCIT was significantly higher in patients with severe AD (90.6%) than patients with mild to moderated AD (63.7%) (p<0.001). Patients with severe AD showing a favorable clinical response had a significantly shorter duration of AD (12.3±8.5 years; mean±SD) than patients with severe AD showing no significant clinical response (20.6±10.9 years) (p<0.05) at baseline.ConclusionSCIT could be a clinically useful therapeutic option for patients with severe AD sensitized to HDM. Early initiation of SCIT might provide a favorable clinical outcome in patients with severe AD sensitized to HDM.

Effect of heat denaturation of egg white proteins ovalbumin and ovomucoid on CD4+ T cell cytokine production and human mast cell histamine production

The conformational epitopes of egg glycoproteins ovalbumin (OVA) and ovomucoid (OVM) recognized by IgE antibodies in an allergic response can be denatured at high temperatures. This structural change results in a decreased allergenicity and has earlier been used to induce clinical tolerance for specific oral immunotherapy in allergic patients via consumption of cooked egg products. We investigated the difference in allergic response when consuming heat-treated and native egg proteins by examining the cytokine production of CD4+ T cells and mast cell histamine release. Cultures of mouse CD4+ T cells and dendritic cells were stimulated with native and heat denatured OVA and OVM (HD-OVA and HD-OVM) and various cytokine and histamine concentrations were measured using ELISA. An increased concentration of IL-12, IL-17 and IL-10 and a decreased concentration of IL-4 were detected in both HD-OVA and HD-OVM (p < 0.05). A decreased concentration of histamine was detected in HD-OVM (p < 0.05) with human KU812 basophil like cells. Heat denatured egg proteins OVA and OVM demonstrated a skewed type 1 CD4+ T cell cytokine response and inhibited intracellular Ca2+ concentration. This study provides insights into understanding the mechanisms behind induced tolerance of allergic individuals when consuming cooked egg.

Immunotherapy in all aspects.

Allergen immunotherapy is a form of long-term treatment that decreases symptoms for many people with allergic rhinitis, allergic asthma, conjunctivitis (eye allergy) or stinging insect allergy. In this review, we presented the important topics in immunotherapy. The important aspects of immunotherapy are considered to be "Immunologıcal responses to immunotherapy"; "The principal types of immunotherapy"; "Effectiveness"; "Indications"; "Contraindications"; "Allergen immunotherapy in children"; "Safety"; and "Anaphylactic reactions after immunotherapy". The principal types of immunotherapy are subcutaneous immunotherapy (SCIT) and sublingual immunotherapy. Both of them can be used in indicated cases. When using SCIT, physicians must be more careful because of reported rare fatal cases. The risks and benefits of continuing allergen immunotherapy in patients who have experienced severe systemic reactions should be carefully considered.

Safety and Efficacy of Allergen Immunotherapy in Patients with HIV and Allergic Rhinitis: Facts and Fiction

Allergic disorders are increasing, and more than a quarter of the global population have allergies. The belief that individuals infected with human immunodeficiency virus (HIV) are less likely to develop allergic disorders has been disproved. Approximately 33.3 million individuals younger than 25 years of age are living with HIV. Allergic rhinitis is a poorly controlled, chronic disorder in this group of patients. The burden of disease related to allergic rhinitis, both personal and global, has challenged the experts in the field to improve currently available treatments. Allergen immunotherapy is the only recognised treatment which can modulate the immune system and develop tolerance. It has been available for the past 100 years, and although improvements have been made to make it more effective and a relatively safe treatment option, it is poorly used for treating patients with HIV who have allergic rhinitis. This article explores the limited information available in the literature to help highlight the urgent need to address this issue which remains a complex management dilemma for physicians.

PRS59 - Cost-Effectiveness Analysis of Allergen Immunotherapy in Patients With Grass Pollen-Induced Allergic Rhinitis in Spain

PRS59 - Cost-Effectiveness Analysis of Allergen Immunotherapy in Patients With Grass Pollen-Induced Allergic Rhinitis in Spain

Low-Allergenic Hydrolyzed Egg Induces Oral Tolerance in Mice

Background: Egg allergy is one of the most common food allergies in children. The standard therapy for egg allergy is strict avoidance. Yet, there is considerable clinical and scientific interest in primary or secondary prevention. A major drawback of oral tolerance (OT) induction protocols, however, is the possibility of severe side effects; thus, we have formulated a hypoallergenic egg product and demonstrate its in vivo capacity to modulate the immune system in the current study. Methods: Hydrolyzed egg (HE) was produced using a combination of moderate heat treatment and enzymatic hydrolysis. The capacity of HE to induce OT was tested in experimental models and compared to whole egg (WE). Delayed-type hypersensitivity (DTH) responses, immune markers and potential early markers of OT were analyzed. Results: Allergic responses, assessed by both DTH responses upon OVA challenge and serum OVA-specific IgE and IgG1, were decreased after treatment with HE and WE compared to the control group. Additionally, feeding WE and HE significantly decreased Th2 cytokine induction and cell proliferation, induced the activation of effector CD4+ T cells and increased numbers and percentages of ICOS+CD4+CD25+Foxp3+ cells. Furthermore, DO11.10 mouse experiments showed that HE contains other peptides than the OVA_323-339 peptide that are able to induce tolerance to OVA. Conclusions: Altogether, results showed that HE induces OT in mice in a dose-dependent manner. Due to its low allergenicity compared to WE, it may represent a safer alternative for OT induction in at-risk subjects or oral immunotherapy in allergic patients.

T helper cells plasticity in inflammation

CD4+ T cells can be subdivided from a functional point of view into two main subsets: effector cells, which provide protection against exogenous offending agents, and regulatory T (Treg) cells whose function is to avoid autoimmune reactions and to stop the effector response against exogenous antigens, when the response itself becomes dangerous for the host. Human effector CD4+ T lymphocytes can be additionally classified into lineages based mainly on their immunological functions that are supported by distinct profile of cytokine, transcription factor, and homing receptors expression. In the last years, beyond the well known populations of human T helper (Th) lymphocytes, Th1 and Th2 cells, other populations have been discovered and phenotypically characterized. These include the Th17 subset, which is certainly the most intensively studied, but also Th22, Th9, and T follicular helper (Tfh) lymphocytes. In addition to their protective functions, these T helper populations are also involved in the pathogenesis of several inflammatory immune-mediated disorders. Th1 and Th17 cells are involved in the pathogenesis of organ-specific autoimmune diseases and other chronic inflammatory disorders, whereas allergen-specific Th2 lymphocytes play a crucial role in allergy. Although classically viewed as distinct lineages, recent evidence indicate that CD4+ T cells, particularly the Th17 subset, are more plastic than previously thought. It is not fully understood how often such plasticity occurs in the course of physiologic responses to pathogens and what its importance is in protective immunity, but in inflammatory conditions Th17 lymphocytes that have shifted towards a Th1 or Th2 phenotype, acquiring the ability to produce IFN-γ or IL-4, and seem to be particularly aggressive and more pathogenic than the unshifted cells. In this context, the possibility to interfere with this modulation of phenotype can be considered a possible target for developing novel therapeutic strategies in the above mentioned diseases.

Omalizumab and hypersensitivity reactions

Omalizumab, a monoclonal anti-IgE antibody, is currently indicated for the treatment of moderate-to-severe allergic asthma. We have reviewed the published studies and case reports of off-label omalizumab use in the prevention of IgE-mediated hypersensitivity reactions of various causes. Additionally, we have reviewed anaphylaxis associated with omalizumab treatment. Many case reports and smaller studies have reported the efficacy of omalizumab in the prevention of various hypersensitivity and anaphylactic reactions with or without known trigger. One randomized study has showed partial improvement in the tolerance of peanuts in peanut-allergic patients with anti-IgE therapy. Furthermore, several randomized, placebo-controlled studies and case reports have demonstrated that omalizumab in combination with allergen or venom immunotherapy decreases the incidence of systemic hypersensitivity reactions and may improve the clinical outcomes. Finally, review of the data documents low risk of anaphylaxis with omalizumab use, with one study demonstrating successful desensitization to this medication. The available studies indicate that omalizumab is effective and well tolerated in decreasing hypersensitivity reactions associated with allergen immunotherapy in patients with allergic rhinitis and mild-to-moderate asthma. Additionally, omalizumab may represent a promising therapy of anaphylaxis with or without known trigger, which should be further investigated with randomized studies. Moreover, additional research is needed to elucidate the mechanism of anaphylaxis with the medication itself.

Validation of the first treatment-specific questionnaire for the assessment of patient satisfaction with allergen-specific immunotherapy in allergic patients: The ESPIA questionnaire

Satisfaction with treatment is a patient-reported outcome shown to be associated with the patient's health-related decisions and treatment-related behavior, thereby influencing the chances of successful treatment, and is especially relevant in long-term treatment, such as allergen-specific immunotherapy (AIT). We sought to assess the psychometric properties of the Satisfaction Scale for Patients Receiving Allergen Immunotherapy (ESPIA) questionnaire so as to determine the satisfaction of patients receiving AIT treatment. An observational, longitudinal, multicenter study was performed on patients with allergic rhinitis (AR) undergoing AIT treatment. Sociodemographic, clinical, and patient-centered health outcomes data were gathered at the study visits. Feasibility, reliability, validity, and sensitivity to change of the prevalidated version of the ESPIA questionnaire were assessed. Four hundred twenty-nine patients were included (52.2% women, 33.6 years of age, 54.5% of the cases with intermittent AR and 62.5% with moderate AR). Low levels of missing items and ceiling/floor effects were found for the overall score of the ESPIA questionnaire. The overall Cronbach α value and intraclass correlation coefficient were 0.90 and 0.92, respectively. The overall score for the ESPIA questionnaire was strongly associated with months receiving AIT, AR type and intensity, presence of conjunctivitis, self-perceived health status, effect of AR on daily life, and expectations about the AIT treatment. The pattern of correlations obtained with other patient-centered health outcomes was consistent with expectations. The ESPIA questionnaire also showed good sensitivity to change for improved health status. The ESPIA questionnaire to assess patient satisfaction with respect to AIT treatment presented satisfactory psychometric properties for its use in clinical practice.

Hyaluronidase from the venom of the social wasp Polybia paulista (Hymenoptera, Vespidae): Cloning, structural modeling, purification, and immunological analysis

In this study, we describe the cDNA cloning, sequencing, and 3-D structure of the allergen hyaluronidase from Polybia paulista venom (Pp-Hyal). Using a proteomic approach, the native form of Pp-Hyal was purified to homogeneity and used to produce a Pp-specific polyclonal antibody. The results revealed that Pp-Hyal can be classified as a glycosyl hydrolase and that the full-length Pp-Hyal cDNA (1315 bp; GI: 302201582) is similar (80–90%) to hyaluronidase from the venoms of endemic Northern wasp species. The isolated mature protein is comprised of 338 amino acids, with a theoretical pI of 8.77 and a molecular mass of 39,648.8 Da versus a pI of 8.13 and 43,277.0 Da indicated by MS. The Pp-Hyal 3D-structural model revealed a central core (α/β)7 barrel, two sulfide bonds (Cys 19–308 and Cys 185–197), and three putative glycosylation sites (Asn79, Asn187, and Asn325), two of which are also found in the rVes v 2 protein. Based on the model, residues Ser299, Asp107, and Glu109 interact with the substrate and potential epitopes (five conformational and seven linear) located at surface-exposed regions of the structure. Purified native Pp-Hyal showed high similarity (97%) with hyaluronidase from Polistes annularis venom (Q9U6V9). Immunoblotting analysis confirmed the specificity of the Pp-Hyal-specific antibody as it recognized the Pp-Hyal protein in both the purified fraction and P. paulista crude venom. No reaction was observed with the venoms of Apis mellifera, Solenopsis invicta, Agelaia pallipes pallipes, and Polistes lanio lanio, with the exception of immune cross-reactivity with venoms of the genus Polybia (sericea and ignobilis). Our results demonstrate cross-reactivity only between wasp venoms from the genus Polybia. The absence of cross-reactivity between the venoms of wasps and bees observed here is important because it allows identification of the insect responsible for sensitization, or at least of the phylogenetically closest insect, in order to facilitate effective immunotherapy in allergic patients.

Uncontrolled allergic rhinitis and chronic rhinosinusitis: where do we stand today?

State-of-the-art documents like ARIA and EPOS provide clinicians with evidence-based treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS), respectively. The currently available medications can alleviate symptoms associated with AR and RS. In real life, a significant percentage of patients with AR and CRS continue to experience bothersome symptoms despite adequate treatment. This group with so-called severe chronic upper airway disease (SCUAD) represents a therapeutic challenge. The concept of control of disease has only recently been introduced in the field of AR and CRS. In case of poor control of symptoms despite guideline-directed pharmacotherapy, one needs to consider the presence of SCUAD but also treatment-related, diagnosis-related and/or patient-related factors. Treatment-related issues of uncontrolled upper airway disease are linked with the correct choice of treatment and route of administration, symptom-oriented treatment and the evaluation of the need for immunotherapy in allergic patients. The diagnosis of AR and CRS should be reconsidered in case of uncontrolled disease, excluding concomitant anatomic nasal deformities, global airway dysfunction and systemic diseases. Patient-related issues responsible for the lack of control in chronic upper airway inflammation are often but not always linked with adherence to the prescribed medication and education. This review is an initiative taken by the ENT section of the EAACI in conjunction with ARIA and EPOS experts who felt the need to provide a comprehensive overview of the current state of the art of control in upper airway inflammation and stressing the unmet needs in this domain.

Tolerance induction with T cell–dependent protein antigens induces regulatory sialylated IgGs

Under inflammatory conditions, T cell-dependent (TD) protein antigens induce proinflammatory T- and B-cell responses. In contrast, tolerance induction by TD antigens without costimulation triggers the development of regulatory T cells. Under both conditions, IgG antibodies are generated, but whether they have different immunoregulatory functions remains elusive. It was shown recently that proinflammatory or anti-inflammatory effector functions of IgG molecules are determined by different Fc N-linked glycosylation patterns. We sought to examine the Fc glycosylation and anti-inflammatory quality of IgG molecules formed on TD tolerance induction. We administered chicken ovalbumin (OVA) with or without costimulus to mice and analyzed OVA-reactive IgG Fc glycosylation. The anti-inflammatory function of differentially glycosylated anti-OVA IgGs was further investigated in studies with dendritic cell cultures and in an in vivo model of allergic airway disease. Additionally, we analyzed the Fc glycosylation pattern of birch pollen-reactive serum IgGs after successful allergen-specific immunotherapy in patients. Stimulation with TD antigens under inflammatory conditions induces plasma cells expressing low levels of α2,6-sialyltransferase and producing desialylated IgGs. In contrast, plasma cells induced on tolerance induction did not downregulate α2,6-sialyltransferase expression and secreted immunosuppressive sialylated IgGs that were sufficient to block antigen-specific T- and B-cell responses, dendritic cell maturation, and allergic airway inflammation. Importantly, successful specific immunotherapy in allergic patients also induced sialylated allergen-specific IgGs. Our data show a novel antigen-specific immunoregulatory mechanism mediated by anti-inflammatory sialylated IgGs that are formed on TD tolerance induction. These findings might help to develop novel antigen-specific therapies for the treatment of allergy and autoimmunity.

Cost-Effectiveness of Allergen Immunotherapy

The current burden of allergic diseases, considering both direct and indirect costs, is very relevant. In fact the estimated cost for allergic rhinitis (AR) is 4-10 billion dollars/year in the US and averages an annual cost of 1089 euros per child/adolescent and 1543 euros per adult in Europe. The cost is obviously higher when including also allergic asthma. Strategies aimed at reducing the clinical severity of allergy are therefore most relevant from both a societal and healthcare system’s perspective. Among them, allergen immunotherapy (AIT) showed preventive capacity and also a carryover effect once treatment is discontinued, thus further reducing the costs. A number of studies demonstrated a favorable cost-benefit ratio for AIT. The first studies in the 1990s evaluating subcutaneous AIT in patients with allergic rhinitis and asthma, reported significant reductions of direct and indirect costs in subjects treated with AIT, as compared to those treated with symptomatic drugs. This was fully confirmed in recent studies conducted in European countries, also including sublingual immunotherapy, as well as in studies conducted in the US. In particular, the conclusion of a recent study on health care cost benefits of AIT in children with AR suggesting that “Greater use of this treatment in children could significantly reduce AR-related morbidity and its economic burden” should be kept in mind when considering the optimal choice of medical treatment in patients with AR or asthma.

Cross-reactivity of pollen and food allergens: soybean Gly m 4 is a member of the Bet v 1 superfamily and closely resembles yellow lupine proteins

In many cases, patients allergic to birch pollen also show allergic reactions after ingestion of plant-derived food. This observation is explained on the molecular level by cross-reactivity of IgE antibodies induced by sensitization to the major birch pollen allergen Bet v 1 with homologous food allergens. As IgE antibodies recognize conformational epitopes, a precise structural characterization of the allergens involved is necessary to understand cross-reactivity and thus to develop new methods of allergen-specific immunotherapy for allergic patients. Here we present the three-dimensional solution structure of the soybean allergen Gly m 4, a member of the superfamily of Bet v 1 homologous proteins and a cross-reactant with IgE antibodies originally raised against Bet v 1, as shown by immunoblot inhibition and histamine release assays. Although the overall fold of Gly m 4 is very similar to that of Bet v 1, the three-dimensional structures differ in detail. The Gly m 4 local structures that display those differences are also found in proteins from yellow lupine. The three-dimensional structure of Gly m 4 in combination with immunological data allows us to propose surface patches that might represent cross-reactive epitopes.

Role of immunmodulators in allergen-specific immunotherapy

Allergen-specific immunotherapy (SIT) is the only causal treatment of allergic disorders and therefore a cornerstone in the management of respiratory allergy. SIT is effective in patients with allergic rhinitis and mild-to-moderate allergic asthma. Successful treatment is associated with decrease in allergic symptoms of the upper and lower airways. The most relevant limitation in the daily routine is the restricted use of SIT in patients with moderate-to-severe allergic asthma. A strategy to overcome this limitation is to combine SIT with immunmodulators. One example of a recently developed immunmodulator is Omalizumab, a humanized, monoclonal anti-IgE antibody that binds to circulating IgE molecules, thus interrupting the allergic cascade downstream the IgE production of B cells. Up to now, four clinical trials have been performed, which all showed that the combination of Omalizumab and SIT is safe and clinically more effective than SIT alone. Moreover, administration of Omalizumab prior to SIT reduces the risk of SIT-related systemic reactions. Omalizumab and SIT are also effective in patients with mild-moderate allergic asthma. In conclusion, the use of Omalizumab as an additive immunmodulator improves safety and efficacy and might be a useful approach to broaden the indication of specific immunotherapy in allergic patients.