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Introduction: Eosinophilic esophagitis (EoE) is a chronic esophageal atopic disease because sensitization to aeroallergens and foods allergens is very common.Objectives: This study is the first work that studies multiple characteristics of EoE in the southeast of Spain to know whether EoE in the patients of this region is similar to that of other regions of Spain in terms of demography, symptoms, and atopic characteristics.Method: It is an observational prospective study of patients diagnosed with EoE at Granada (Spain). We recorded demographic data (age, sex, and personal history of atopy), clinical data (impaction and dysphagia), allergologic data (prick test and specific immunoglobulin E) to foods, aeroallergen, and pan-allergens, and other endoscopic–histologic data andcomorbidities.Results: The demographic, allergologic, and endoscopic characteristics of patients with EoE in Granada were similar to the rest of Spain, except the higher frequency of sensitization to olive pollen, food allergy, and anaphylaxis reactions.Conclusions: The higher frequency of sensitization to olive pollen and food allergy with severe clinical manifestations (anaphylaxis) in patients with EoE in Granada could have a negative impact on patients’ quality of life.

Background: As the number of allergic sensitizations increases the severity of allergic respiratory diseases worsens. Multiple monoallergen immunotherapy can be accompanied by poor treatment adherence and high costs, single multiallergen immunotherapy needs to prove efficacy whilst maintaining a good safety profile. Methods: Observational, retrospective, multicenter study using a 2-pollen single undiluted multiallergen subcutaneous immunotherapy (SCIT) in routine clinical practice in Spain. Patients with rhinoconjunctivitis, with/without controlled asthma, sensitized to grass, olive, Parietaria, Cupressus, plane tree and/or Salsola pollen were included. Primary and secondary clinical efficacy endpoints were quality of life (mini Rhinitis Quality of Life Questionnaire (miniRQLQ)) and visual analogue scale (VAS) respectively. All adverse events were documented. Results: Ten centers included 97 patients, median age 32 years. SCIT treatment included combinations of grass mix with olive, Parietaria, Cupressus, plane tree or Salsola or olive with Parietaria, Cupressus or Salsola. The mean duration of SCIT was 1.8 years with a high treatment adherence (73%). Significant improvement in quality of life, nasal and ocular symptoms, activity limitations and practical problems (p< 0.0001) and other symptoms (p= 0.024) was observed. Most patients did not develop asthma-like symptoms and a significant improvement of all allergic symptom severity was perceived. VAS showed a significant improvement in rhinoconjunctivitis and asthma by patients and physicians. Twenty-nine patients experienced adverse reactions, 25 had local and 6 had systemic reactions. Conclusions: Single undiluted multiallergen SCIT treatment of two different pollens is efficacious and safe in both children and adults, showing that it is a suitable option for the treatment of polyallergic patients.

Empirical evidence suggests that the effects of anthropogenic climate change, and heat in particular, could have a significant impact on mental health. This article investigates the correlation between heatwaves and/or relative humidity and suicide (fatal intentional self-harm) on a global scale. The covariance between heat/humidity and suicide was modelled using a negative binomial Poisson regression with data from 60 countries between 1979–2016. Statistically significant increases and decreases in suicide were found, as well as many cases with no significant correlation. We found that relative humidity showed a more significant correlation with suicide compared to heatwaves and that both younger age groups and women seemed to be more significantly affected by changes in humidity and heatwave counts in comparison with the rest of the population. Further research is needed to provide a larger and more consistent basis for epidemiological studies; to understand better the connections among heat, humidity and mental health; and to explore in more detail which population groups are particularly impacted and why.

Empirical evidence suggests that the effects of anthropogenic climate change, and heat in particular, could have a significant impact on mental health. This article investigates the correlation between heatwaves and/or relative humidity and suicide (fatal intentional self-harm) on a global scale. The covariance between heat/humidity and suicide was modelled using a negative binomial Poisson regression with data from 60 countries between 1979-2016. Statistically significant increases and decreases in suicide were found, as well as many cases with no significant correlation. We found that relative humidity showed a more significant correlation with suicide compared to heatwaves and that both younger age groups and women seemed to be more significantly affected by changes in humidity and heatwave counts in comparison with the rest of the population. Further research is needed to provide a larger and more consistent basis for epidemiological studies; to understand better the connections among heat, humidity and mental health; and to explore in more detail which population groups are particularly impacted and why.

Asthma is a complex, chronic respiratory disease with a wide clinical spectrum. Use of high-throughput technologies has generated a great deal of data that require validation. In this work the objective was to validate molecular biomarkers related to asthmatic disease types in peripheral blood samples and define their relationship with disease severity. With this purpose, ninety-four previously described genes were analyzed by qRT-PCR in 30 healthy control (HC) subjects, 30 patients with nonallergic asthma (NA), 30 with allergic asthma (AA), and 14 patients with allergy (rhinitis) but without asthma (AR). RNA was extracted from peripheral blood mononuclear cells (PBMCs) using the TRIzol method. After data normalization, principal component analysis (PCA) was performed, and multiple approaches were used to test for differential gene expression. Relevance was defined by RQ (relative quantification) and corrected P value (

Background Allergy to olive pollen is one of the primary causes of allergic asthma in Spain. Even though allergen immunotherapy (AIT) has shown clinical benefits in patients sensitized to different allergens, studies in asthmatic patients sensitized to olive pollen are insufficient. Objective To assess the effectiveness and safety of an ultra-short course of AIT with an L-tyrosine-adsorbed and monophosphoryl lipid A-adjuvanted olive pollen and olive/grass pollen extract (Pollinex Quattro®) in patients with allergic asthma in the real-world setting. Methods Retrospective, controlled study including patients with asthma, with and without allergic rhinitis, caused by sensitization to olive pollen from 11 centers in Spain. Patients received out-of-season (October–March) treatment with AIT in addition to their pharmacological treatment (active group) or pharmacological treatment (control group). Effectiveness variables, including unscheduled visits to the healthcare center, emergency room admissions, symptoms of asthma and rhinitis (following GEMA and ARIA classifications, respectively), and use of medication to treat asthma and rhinitis during the subsequent pollen season were compared between treatment groups. Results Of 131 study patients, 42 were treated with their usual asthma medication (control group) and 89 were treated with AIT (active group), either Pollinex Quattro® 100% olive pollen (n = 43, 48.3%) or 50% olive pollen/50% grass pollen (n = 46, 51.7%). Patients’ demographic and clinical characteristics were similar between groups. The mean (SD) number of unscheduled visits to a healthcare center and emergency room admissions due to allergy symptoms was 2.19 (1.40) and 0.43 (0.63) in the control group, and 1.09 (1.25) and 0.11 (0.51) in the active group (P = 0.001 and P = 0.006, respectively). Severity and control of asthma symptoms remained unchanged (P = 0.347 and P = 0.179, respectively), rhinitis type improved (P = 0.025), and severity remained unchanged in the active compared to the control group. The use of short-acting beta-agonists and inhaled corticosteroids to treat asthma symptoms decreased in the active vs. the control group (P = 0.001 and P = 0.031, respectively). Twelve (13.5%) and two (2.2%) patients in the active group experienced local adverse reactions (edema, swelling, erythema, hives, pruritus, and heat), and systemic adverse reactions (hypertensive crisis and low-grade fever) to AIT, respectively; none was serious. Conclusion AIT with Pollinex Quattro® specific for olive pollen and olive/grass pollens resulted in reduced visits to the healthcare center and emergency room and the use of asthma medication during the pollen season, indicating that this treatment was safe and effective in treating asthma in patients sensitized to these pollens.

Olive-pollen allergy is one of the leading causes of respiratory allergy in Mediterranean countries and some areas of North America. Currently, allergen-specific immunotherapy is the only etiophatogenic treatment. However, this approach is not fully optimal, safe, or effective. Thus, efforts continue in the search for novel immunotherapy strategies, being one of the most promising the use of peptides derived from major allergens. This work tries to determine the therapeutic potential and safety of 5 dodecapeptides derived from the main allergen of olive-pollen allergy, Ole e 1. The immunomodulatory capacity of these peptides was studied using peripheral blood mononuclear cells (PBMCs) obtained from 19 olive-pollen-allergic patients and 10 healthy controls. We determined the capacity of these peptides to inhibit the proliferative response toward olive-pollen allergenic extract and to induce the regulatory cytokines, IL-10 and IL-35. To test the safety and absence of allergenicity of the peptides, the basophil activation was analyzed by flow-cytometry, using peripheral blood. The results showed that two of five peptides inhibited near to 30% the proliferative response against the total olive-pollen allergenic extract in olive-pollen-allergic patients. Inhibition increased to nearly 35% when the 5 peptides were used in combination. In both cases, a statistically significant induction of IL-10 and IL-35 secretion was observed in the supernatants of allergic patients PBMCs cultures. None of the 5 peptides induced basophil activation and cross-link inflammatory cell-bound IgE. In conclusion, these results open up new possibilities in the treatment of olive-pollen allergy, which could solve some of the problems facing current therapy approaches, Supported by research grants PI13/01730, PI17/01682 cofinanced by FEDER, CIBERES (ISCIII, 0013), and RETIC (RD09/0076/00101) from the Fondo de Investigación Sanitaria (Ministerio de Sanidad y Consumo, Spain). D. Calzada was supported by a contract from Comunidad de Madrid (PEJD-2016/BMD- 2682, Sistema de Garantía Juvenil), L. Cremades-Jimeno was supported by a contract from MINECO (PEJ-2014-A-31609, Sistema de Garantía Juvenil) and MA. de Pedro was supported by a contract from Comunidad de Madrid (PEJ-2017-AI/SAL-5938, Sistema de Garantía Juvenil), all cofinanced by Fondo Social Europeo (FSE) and Iniciativa de Empleo Juvenil (IEJ). S. Baos was supported by Fundación Conchita Rábago and PI17/01682.

Two regions of Ole e 1, the major olive-pollen allergen, have been characterized as T-cell epitopes, one as immunodominant region (aa91-130) and the other, as mainly recognized by non-allergic subjects (aa10-31). This report tries to characterize the specific relevance of these epitopes in the allergic response to olive pollen by analyzing the secreted cytokines and the gene expression profiles induced after specific stimulation of peripheral blood mononuclear cells (PBMCs). PBMCs from olive pollen-allergic and non-allergic control subjects were stimulated with olive-pollen extract and Ole e 1 dodecapeptides containing relevant T-cell epitopes. Levels of cytokines were measured in cellular supernatants and gene expression was determined by microarrays, on the RNAs extracted from PBMCs. One hundred eighty-nine differential genes (fold change >2 or

Hemos leído con interés el artículo publicado en su revista sobre la ingesta dietética en pacientes con esofagitis eosinofílica, tratada con dieta empírica de seis alimentos. En este trabajo, se objetivan las carencias nutricionales de los pacientes que siguen esta dieta, déficit observable desde su descripción en Estados Unidos hace unos 12 años, por lo que se la considera actualmente contraproducente como terapéutica, así como por su agresividad, al precisar gran número de endoscopias, lo cual la convierte en poco factible en la práctica clínica habitual. Por esta razón, se han diseñado otro tipo de dietas. En contraposición al artículo, la EE es una patología caracterizada por una reacción inmunoalérgica mediada por Th2 (5) en la que el reflujo gastroesofágico no es excluyente, sino que puede coexistir (2) e incluso contribuir a la patogénesis aumentando el daño esofágico y la respuesta inmunoalérgica, sobre todo en sus estadios iniciales (2).

β-conglutin has been identified as a major allergen for Lupinus angustifolius seeds. The aim of this study was to evaluate the binding of IgE to five recombinant β-conglutin isoforms (rβ) that we overexpressed and purified and to their natural counterparts in different lupin species and cultivars. Western blotting suggested β-conglutins were the main proteins responsible for the IgE reactivity of the lupin species and cultivars. Newly identified polypeptides from “sweet lupin” may constitute a potential new source of primary or cross-reactive sensitization to lupin, particularly to L. albus and L. angustifolius seed proteins. Several of them exhibited qualitative and quantitative differences in IgE-binding among these species and cultivars, mainly in sera from atopic patients that react to lupin rather than peanut. IgE-binding was more consistent to recombinant β2 than to any of the other isoforms, making this protein a potential candidate for diagnosis and immunotherapy., This work was supported by the European Research Program MARIE CURIE (FP7-PEOPLE-2011-IOF) for the grant ref. number PIOF-GA-2011-301550 to JCJ-L, KBS and JDA. JCJ-L and JDA thank the Spanish Ministry of Economy, Industry and Competitiveness for the grants ref. number RYC-2014-16536 (Ramon y Cajal Research Program), BFU2016-77243-P, RTC-2015-4181-2 and RTC-2016-4824-2. Authors thank W. Smith (Royal Adelaide Hospital), M. Stuckey (St John of God Pathology) and R. Loblay (Royal Prince Alfred Hospital) for providing sera and L. Wienholt (Royal Prince Alfred Hospital) for doing the ImmunoCAP analysis of lupin- and peanut-specific IgE in some serum.

Olive seeds, which are a raw material of interest, have been reported to contain 11S seed storage proteins (SSPs). However, the presence of SSPs such as 7S vicilins has not been studied. In this study, following a search in the olive seed transcriptome, 58 sequences corresponding to 7S vicilins were retrieved. A partial sequence was amplified by PCR from olive seed cDNA and subjected to phylogenetic analysis with other sequences. Structural analysis showed that olive 7S vicilin contains 9 -helixes and 22 -sheets. Additionally, 3D structural analysis displayed good superimposition with vicilin models generated from Pistacia and Sesamum. In order to assess potential allergenicity, T and B epitopes present in these proteins were identified by bioinformatic approaches. Different motifs were observed among the species, as well as some species-specific motifs. Finally, expression analysis of vicilins was carried out in protein extracts obtained from seeds of different species, including the olive. Noticeable bands were observed for all species in the 15–75 kDa MW interval, which were compatible with vicilins. The reactivity of the extracts to sera from patients allergic to nuts was also analysed. The findings with regard to the potential use of olive seed as food are discussed. [EN], This study has been supported by the following grants, partially cofunded by ERDF: P2010-AGR-6274 and P2011-CVI-7487 from the Junta de Andalucía; the 201540E065 Intramural-CSIC and MINECO RETOS-COLABORACIÓN RTC2015-4181-2; and the EU Marie Curie (FP7-PEOPLE-2011-IOF) ref. PIOF-GA-2011-311550.

Background: The major antigen of olive tree pollen, Ole e 1, produces an IgE response restricted by DQ2. Objective: Our purpose was to further analyze the genetic restrictions associated with IgE and IgG antibodies against Ole e 1 and IgE against the recently described antigen Ole e 3. Methods: Twenty-two nuclear olive pollen–allergic families (n = 88) were selected. DRB1 and DQB1, TCR-Vα 8.1, the high-affinity receptor of IgE (FcϵRI-β) Rsa I exon 7 and intron 2 and TNF-β (LTα– Nco I) polymorphisms were determined by PCR and analyzed for association with allergic traits by the multiallelic transmission disequilibrium test. Results: Significant associations were found among HLA-DQB1*0201 (n = 29) and high levels of IgG ( P = .023) and IgE ( P = .0136) antibodies to Ole e 1 and with IgE specific to Ole e 3 ( P = .0368). DRB1*0701 was associated with high levels of total serum IgE ( P = .04) and IgG against Ole e 1 ( P = .025). The FcϵRI-β Rsa I exon 7, allele 1 (n = 39), was associated with high levels of total serum IgE ( P = .01), IgE antibodies against Olea europaea extract ( P = .004), and specific antibodies to Ole e 1, IgG ( P = .04), and IgE ( P = .006). The FcϵRI-β Rsa I intron 2, allele 2 (n = 33), was associated with IgE antibodies to O europaea extract ( P = .003) and specific antibodies to Ole e 1, IgG ( P = .025), and IgE ( P = .05). Conclusions: We found a new association between IgE antibody response to Ole e 3 and DQB1*0201 and verified the previously reported association between Ole e 1–specific response and DQB1*0201. Also, the association between FcϵRI-β and IgE antibodies against Ole e 1 was demonstrated. (J Allergy Clin Immunol 2000;105:292-8.)

Background The amino-acid and nucleotide sequence of Ole e 1 (the major antigen of olive pollen) has been described and the IgE antibody response to this major allergen was associated with DR7/DQ2 antigens. With this previous data we try to define the T-cell epitopes implicated in Ole e 1 reactivity. Objectives To study the recognition of T cells (derived from allergic and non-allergic Ole e 1 patients) to Ole e 1 synthetic peptides in order to define immunodominant T-cell epitopes. Methods We have compared the proliferative response of the peripheral blood mononuclear cells from Ole e 1 sensitized patients vs. non-sensitized controls, induced by 14 Ole e 1 synthetic peptides. Thirty subjects were classified in two groups: group 1 (non-responders against Ole e 1, n = 16) and group 2 (Ole e 1 responders, n = 14), according to their clinical parameters and the presence or not in their sera of the significant Ole e 1 IgE antibody levels. Results Our results shown that it is possible to find T cells reactive to Ole e 1 peptides in patients with and without significant levels of Ole e 1 IgE antibodies. However, the percentage of response was higher in patients with IgE antibodies 71.4% vs 25%), and the recognition profile was different: the control group showed a broad reactivity pattern, in contrast, the response by the ‘Ole e 1 responders’ group was mainly directed against three peptides of the carboxi-terminal region, peptides 10 (91–102), 12 (109–120) and 13 (119–130), with a response frequency of 35.7, 28.5 and 28.5%, respectively. By direct and inhibition test no antibody response was found against the synthetic peptides. Conclusions Our data suggest that the regions between 91 and 102 and 109–130 amino-acids on the Ole e 1 molecule are immunodominant T-cell epitopes. These epitopes are not recognized by IgE antibodies.

Standardization of protein extracts for clinical purposes represents an important task in order to maintain adequate reactivity, presence of the relevant allergens and safety among other factors. The main objective of this work was to explore the potential use of a chip-based automated capillary electrophoresis system commercially available to analyze several of the most common forms of allergenic extracts from olive pollen used in allergy clinics. These include experimental extracts prepared from olive pollens, in-house reference extracts, extracts designed for skin prick test assays, and a panel of vaccine variants aimed to specific immunotherapy. As a major conclusion of the study, chip-based capillary electrophoresis allowed in all cases to determine accurate protein profiles with different degrees of sensitivity, where several allergens (particularly the major olive pollen allergen Ole e 1) were easily recognized. Moreover, several purified allergens were also analyzed by this method, and proposed as specific standards for different purposes. In the present condition, the method can only provide the protein profile of the extracts respect to a pre-established standard extract, but not allergen identification. However, these and other future developments and applications are discussed. This work was supported by European Regional Development Fund (ERDF)-cofunded projects BFU2011-22779, P2010-AGR6274, P2010-CVI5767 and P2011-CVI-7487.

Different molecular mechanisms may modulate sensitization and natural or induced tolerance to allergens. We have searched for differential mechanisms at humoral and cellular level in the olive pollen allergic response, checking the influence of exposure to allergens of subjects from an area with extremely high antigenic load during the pollen season. Sera and PBMCs were obtained during and outside the pollen season. Distinct Ig subtypes (total IgE and specific IgE, IgG4 and IgA), and Th1, Th2 and regulatory T cells (Treg) cytokines were analyzed in 5 groups of subjects: Group 1, non-allergic; Group 2, asymptomatic, sensitized to olive pollen; Group 3, allergic to pollen other than olive; Group 4, allergic to olive pollen (not treated); and Group 5, allergic to olive pollen, and getting specific immunotherapy. Asymptomatic subjects showed the highest total IgE levels. The major difference found between untreated and treated subjects was the high levels of non-inflammatory antibodies (IgG4) in treated Patients. The main result of cytokine analyses was the statistically significant decrease in TGF-β levels in untreated olive pollen allergic subjects (pollen season) compared with treated. A significant decrease in forkhead winged-helix transcription factor (FOXP3) mRNA expression (marker of regulatory response) and a lower presence of Treg cells in PBMCs of olive pollen allergic subjects was found. The results Point to a decrease in the cellular regulatory mechanisms mediated by TGF-β and FOXP3 in olive-pollen allergic patients that could be restored after specific-immunotherapy.

Standardization of pollen protein extracts is essential in order to ensure efficiency and safety in allergy diagnosis and immunotherapy. In this paper, we have optimized a multiplex Western blotting method for the simultaneous detection of four olive pollen allergens (Ole e 1, Ole e 2, Ole e 5, and Ole e 9) on a single blot using a monoclonal antibody from mouse and three polyclonal antibodies raised in rabbit. We utilized unconjugated Fab antibody fragments for blocking rabbit primary antibodies, and fluorescence-based detection. These changes allowed an accurate and reliable comparative quantitation of these allergens among pollen-protein samples from six olive cultivars. In addition, we also tested the IgE-binding capacity of these pollen extracts by reprobing the same blot with a pool of sera from eight patients allergic to olive and detection with enzyme conjugated antibodies. A noticeable variability regarding allergen content and IgE-reactivity was found among the olive cultivars analyzed. Moreover, we could easily confirm the identity of some of the IgE-binding proteins by simply overlapping both fluorescence and chemiluminescence images. This method is versatile since it can be applied to other allergogenic plant species and extended to other allergens., This study was supported by ERDF-cofinanced projects BFU 2004-00601/BFI and BFU2008-00629 from Ministerio de Ciencia e Innovación, and ERDF-cofinanced project P06-AGR-01791 from Junta de Andalucía.

This work was funded by ERDF (co)-financed projects P2010-CVI5767, P2010-AGR6274, BFU2011-22779, P2011-CVI-7487 and PEOPLE-IOF/1526.

Background Diagnosis of Alternaria alternata sensitization is hampered by the variability and complexity of fungal extracts, and thus simplification of the diagnostic procedures with purified allergens should be pursued. Objective We sought to compare A alternata extract and purified natural Alt a 1 (nAlt a 1) and recombinant Alt a 1 (rAlt a 1) allergens for their diagnostic value. Methods Forty-two patients allergic to A alternata , 10 atopic patients with negative skin prick test responses to A alternata extract, and 10 healthy subjects were investigated. Skin prick tests and determination of specific IgE levels were performed with nAlt a 1 and 2 different types of rAlt a 1: rbAlt a 1, expressed in Escherichia coli , and ryAlt a 1, expressed in the yeast Yarrowia lipolytica . Results Prevalence for Alt a 1, Alt a 2, and Alt a 11 by IgE dot-blot testing was 98%, 0%, and 15%, respectively, and therefore Alt a 1 was used as a marker for A alternata sensitization. Immunoblotting and inhibition analysis showed no IgE-binding differences between nAlt a 1 and rAlt a 1. The whole group of patients with allergy to A alternata had positive skin test reactions to purified allergens at 100 μg/mL, whereas no false-positive reactions were detected. Natural or ryAlt a 1 elicited a similar response in skin tests compared with A alternata extract, although a reduced reactivity was observed with rbAlt a 1. Specific IgE levels to nAlt a 1 or rAlt a 1 showed significant correlation and similar sensitivity and specificity. Conclusions Alt a 1, either in its natural or recombinant form, is sufficient for a reliable diagnosis of A alternata sensitization and induces skin prick reactivity comparable with that produced by A alternata extract.

Background: Olea europaea pollen is an important cause of seasonal allergic rhinitis and bronchial asthma in southern Spain. For patients allergic to grass pol– len the critical concentration of airborn pollen is 50 grains/m3, but in the case of Olea pollinosis no data is available. Methods: Fifty–six seasonal allergic rhinitis patients (29 in 1994 and 27 in 1995) were included in this study, all of whom lived in Jaen. Daily symptom card were filled in and pollen counts during May and June were performed in both years. A linear regression model was used for analysis of the airborne pollen concentration and the symptom score. Results: Significant correlations among daily counts of Olea pollen and rhinitis symptoms were obtained. Most of our monosensitized patients needed a high Olea pollen concentration in the atmosphere (around 400 grains/m3) to suffer at least from mild allergic rhinitis symptoms. Conclusion: Local conditions with a wide area dedicated to olive tree cultivars result in a high concentration of this pollen in the atmosphere. Monosensitized Olea patients in our area seem to need exceptionally high levels to suffer from allergic symptoms.

Olive tree pollen is one of the most important causes of allergy in the Mediterranean countries. Although the importance of this pollen provoking respiratory allergy is well established and documented, during the last decades, olive trees have been widely planted for ornamental purposes originating a new source of urban air pollution. This fact is one important reason why studies on olive pollen allergy are needed, in order to have more information about the prevention and possible modulation of this kind of sensitization. This article summarizes the advances in the study of genetic restrictions implicated in the susceptibility to the sensitization against the major allergen from this pollen: Ole e 1. Asthma and allergies are complex diseases involving genetic as well as environmental factors. The final clinical picture results from the interaction between genetic factors and environmental stimuli, and in addition, variables such as age, concurrent infections, and physiological factors, could promote differences in susceptibility. Despite this complexity, the allergic diseases are considered as an excellent model for the analysis of the genetic basis of the human immune response (1). The principal advantages are that they are common diseases with increasing prevalence and in addition, they have a well-defined clinical picture and the causative allergens may be identified and characterized so the immune response to them can be identified. The allergic reaction appears to require the interaction of environmental factors with a series of steps, which are genetically regulated. Genetic regulation of IgE responses to specific allergens may differ from that of the general atopic response. Probably, genetic associations are more readily detected with reactions to purified major allergens rather than complex allergen sources. The immunogenetic mechanisms underlying heightened IgE responsiveness seen in atopic diseases may be divided into two types: (a) antigen-specific and (b) nonantigen-specific (2–4).