Novel murine mAbs define specific and cross-reactive epitopes on the latex profilin panallergen Hev b 8.

The production of specific antibodies able to recognize allergens from different sources or block interactions between allergens and antibodies mediating allergic reactions is crucial for developing successful tools for diagnostics and therapeutics. Panallergens are highly conserved proteins present in widely different species, implicated in relevant cross-reactions. The panallergen latex profilin (Hev b 8) has been associated with the latex-food-pollen syndrome. We generated five monoclonal IgGs and one IgE from murine hybridomas against recombinant Hev b 8 and evaluated their interaction with this allergen using ELISA and biolayer interferometry (BLI). Affinity purified mAbs exhibited high binding affinities towards rHev b 8, with KD1 values ranging from 10-10 M to 10-11 M. Some of these antibodies also recognized the recombinant profilins from maize and tomato (Zea m 12 and Sola l 1), and the ash tree pollen (Fra e 2). Competition ELISA demonstrated that some mAb pairs could bind simultaneously to rHev b 8. Using BLI, we detected competitive, non-competitive, and partial-competition interactions between pairs of mAbs with rHev b 8, suggesting the existence of at least two non-overlapping epitopes on the surface of this allergen. Three-dimensional models of the Fv of 1B4 and 2D10 IgGs and docking simulations of these Fvs with rHev b 8 revealed these epitopes. Furthermore, these two mAbs inhibited the interaction of polyclonal IgE and IgG4 antibodies from profilin-allergic patients with rHev b 8, indicating that the mAbs and the antibodies present in sera from allergic patients bind to overlapping epitopes on the allergen. These mAbs can be useful tools for immune-localization studies, immunoassay development, or standardization of allergenic products.

Crystal structure and biochemical characterization of CJP38, a ß-1,3-glucanase and allergen of Cryptomeria japonica pollen.

A 38 kDa ß-1,3-glucanase allergen from Cryptomeria japonica pollen (CJP38) was recombinantly produced in E. coli and purified to homogeneity with the use of Ni-affinity resin. CJP38 hydrolyzed ß-1,3-glucans such as CM-curdlan and laminarioligosaccharides in an endo-splitting manner. The optimum pH and temperature for ß-1,3-glucanase activity were approximately 4.5 and 50 °C, respectively. The enzyme was stable at 30-60 °C and pH 4.0-10.5. Furthermore, CJP38 catalyzed a transglycosylation reaction to yield reaction products with a molecular weight higher than those of the starting laminarioligosaccharide substrates. The three-dimensional structure of CJP38 was determined using X-ray crystallography at 1.5 Å resolution. CJP38 exhibited the typical (ß/α)8 TIM-barrel motif, similar to allergenic ß-1,3-glucanases from banana (Mus a 5) and rubber tree latex (Hev b 2). Amino acid sequence alignment of these proteins indicated that the two-consensus IgE epitopes identified on the molecular surfaces of Mus a 5 and Hev b 2 were highly conserved in CJP38. Their conformations and surface locations were quite similar for these proteins. Sequence and structural conservation of these regions suggest that CJP38 is a candidate allergen responsible for the pollen-latex-fruit syndrome relating to Japanese cedar pollinosis.

The Clinical Relevance of Natural Rubber Latex-Specific IgE in Patients Sensitized to Timothy Grass Pollen.

BACKGROUND: In pollen-allergic patients, cross-reacting allergens including cross-reactive carbohydrate determinants (CCDs) and profilins may result in positive natural rubber latex (NRL)-specific IgE (sIgE) antibody tests but the relationship between this sensitization and clinical NRL type 1 allergy is poorly described. OBJECTIVE: The aims of this study were to determine the frequency and clinical relevance of NRL sIgE in grass pollen-sensitized individuals and to investigate which NRL allergen components these individuals were sensitized to. METHODS: A total of 383 grass-sensitized patients answered questions about NRL allergy symptoms and their stored sera from previous investigations were analyzed for NRL sIgE. Patients with NRL sIgE (n = 32) underwent further investigations comprising medical history, skin prick test with NRL and inhalational allergens, and an additional blood sample. The additional blood samples were analyzed for total IgE and sIgE against NRL, timothy grass, birch, rHev b 1, 3, 5, 6.01, 6.02, 8, 9, 11, rPhl p 12, and MUXF3, which was used as a marker of CCD sensitization. RESULTS: Overall, 9.4% of all grass pollen-sensitized individuals showed IgE sensitization to NRL but only 1.6% had a confirmed type I NRL allergy. CCD and Hev b 8 explained the clinically irrelevant NRL IgE sensitization in 65% of the cases. We found a highly significant correlation between NRL profilin (Hev b 8) sensitization and grass profilin (Phl p 12) sensitization (p < 0.0001). CONCLUSIONS: Data from this study support the hypothesis that in patients with grass pollen sensitization, Hev b 8 mono-sensitization has little or no clinical relevance and is caused by cross sensitization from grass profilin (Phl p 12).

Profilin, a Change in the Paradigm.

Profilin is a protein that is present in all eukaryotic cells and is responsible for cross-reactivity between pollen, latex, and plant foods. It has been classically acknowledged as a minor or nearly irrelevant allergen, although recent data are changing this conception. The objective of this manuscript is to provide a comprehensive review of published data on the role of this ubiquitous allergen in pollen, latex, and plant food allergy. The patterns of recognition of this minor allergen follow a north-south gradient. Although present in all pollens and vegetables, profilin is significantly associated with allergy to grass pollen and to Cucurbitaceae fruits. Heb v 8, the latex profilin, is usually a marker of profilin allergy in plant food-allergic patients, although it has no clinical relevance in latex allergy. Sensitization to profilin jeopardizes the diagnosis of pollen allergy and selection of immunotherapy, and although component-resolved diagnosis can identify its impact, there are no tailored treatments available. In recent years, several new publications have shown how profilin should be taken into account and, under certain circumstances, considered a marker of severity, an allergen capable of inducing respiratory symptoms, and, in its natural purified form, a potential candidate for etiological treatment of food allergy. Current data on profilin strongly support the need for a shift in the previously accepted paradigm for this allergen. More research should be done to assess the real clinical impact of sensitization in specific populations and to develop therapeutic strategies.

Latex proteins from Calotropis procera: Toxicity and immunological tolerance revisited.

Many thousands of plants are disseminated worldwide in traditional and folk medicines based on the belief that their leaves, roots, seeds, bark or secretions, when adequately handled, can treat, alleviate or ameliorate numerous disease symptoms. Calotropis procera (Apocynaceae) is a popular medicinal plant and the claims of this shrub's phytomedicinal properties have been scientifically validated. In this study, further prospects towards the in vivo toxicity and oral immunological tolerance of phytomodulatory proteins isolated from the latex of C. procera are reported. Acute toxicity was determined in mice by oral and intraperitoneal administration of latex proteins (LP) and was followed behavioral, hematological and histological analyses. Oral immunological tolerance to LP was assessed by intraperitoneal immunization in mice that had received LP orally before. Animals given 5000 mg/kg orally exhibited only discrete behavioral alterations and augmentation of monocytes. Death was not notified 14 days after exposure. However, all animals receiving LP 150 mg/kg by i.p. died in 1 h. Death (20%) was documented when LP (75 mg/kg) was given in the peritoneum and signs of harmful effects were observed in the survivors (80%). Oral immunological tolerance was observed in animals previously given LP orally, when they were further immunized/challenged with peritoneal exposure to different doses of LP. This was confirmed by the lowering of IgE and IgG in the serum, IL-4 and IFN-γ in spleen homogenates and the absence of anaphylaxis signs. It is therefore concluded that LP exhibited quite discrete adverse effects when orally administrated at higher concentrations and this route of administration did not stimulate adverse immunological reactions. Instead it was observed immunological tolerance. The present study contributes very important information concerning the safe use of C. procera as a phytotherapeutic agent.

Profilin cross-reactive panallergen causes latex sensitization in the pediatric population allergic to pollen.

BACKGROUND: Component-resolved diagnostics (CRD) has been demonstrated to be an excellent new tool for improving the current diagnosis of allergies, and it allows differentiation between polysensitization and cross-reactivity. OBJECTIVE: To demonstrate the role of cross-reactive pollen allergens in pediatric patients living in areas with large amounts of airborne grass pollen grains who are sensitive to grass pollen and latex. METHODS: Serum samples were obtained from 106 children between 3 and 14 years of age diagnosed with allergies to pollen based on clinical history, skin prick tests, and specific immunoglobulin E (IgE). None of them had allergy symptoms to latex or fruits. From these 106 children, 56 patients revealed positive results to Phleum-specific major allergens but not to cross-reactive allergens. The other 50 patients who showed positive specific IgE to Phleum-specific major allergens and to cross-reactive pollen allergens also showed positive results to latex allergens. CRD was carried out by specific IgE quantification using a fluoro-enzyme immunoassay (ImmunoCAPT System). RESULTS: Results demonstrated a positive significant relationship between the specific IgE to Hev b 8 and Phl p 12 and also between the specific IgE to Hev b 8 and latex extract in the group of patients sensitized to species-specific and cross-reactive Phleum allergens. Positive significant relationships were also found between profilin and avocado or peach sensitizations. No other latex allergens gave positive results. CONCLUSION: The apparent sensitization to latex in pediatric patients allergic to grass pollen is caused by the cross-reactive profilin panallergen; however, it is appears not to be clinically relevant.

Molecular allergens in the diagnosis of latex allergy.

BACKGROUND: Molecular allergens enable the definition of sensitization profiles in allergic patients. AIM: To validate the most helpful allergens for the diagnosis of latex allergy in different clinical situations. METHODS: 130 patients suspected to be allergic to latex with positive IgE against natural rubber latex (NRL) have been studied: 97 were confirmed as latex allergic (among which 55 professionally exposed to latex and 35 with a peranaesthetic anaphylactic shock) and 33 were only sensitized to latex without clinical allergy. Each serum was tested for IgE against 9 recombinant latex allergens and bromelain using Phadia ImmunoCAP 250. RESULTS: rHev b 6.01, 6.02, 2 and 5 were the major allergens in the allergic population. An excellent correlation (94%) was observed between IgE against rHev b 6.01 and latex prick test positivities. IgE against rHev b 1, 3 and 5 were more frequent and their levels significantly higher in patients with peranaesthetic anaphylactic shock. Among the asymptomatic patients (29/33 allergic to pollen), NRL IgE positivity is explained by the presence of anti-rHev b 8 and/or anti-carbohydrate IgE. CONCLUSIONS: rHev b 6.01 and rHev b 5 specific IgE are of major interest to confirm latex allergy diagnosis. rHev b 5 is particularly useful in case of monosensitization where clinical symptoms and latex skin prick tests may be discordant, rHev b1 and rHev b 3 are interesting to document multi-operated and peranaesthetic latex allergy. Finally, rHev b 8 is a helpful marker to highlight latex/pollen cross-reactivity which improves the specificity of the serological tests.

Component-resolved diagnosis from latex allergy by microarray.

BACKGROUND: A positive specific IgE (sIgE) result for latex does not always mirror the clinical situation and is frequently found in individuals without overt latex allergy. OBJECTIVE: We sought to investigate the potential of component-resolved diagnosis (CRD) of latex allergy by microarray and to assess whether the technique allows discriminating genuine allergy from asymptomatic sensitization. METHODS: Twenty-six healthy controls without a history of latex allergy with a negative latex sIgE and skin test, 22 latex-allergic patients with a compelling history of latex allergy with a positive latex sIgE and prick test and 20 latex-sensitized individuals with a frequent asymptomatic exposure to natural rubber latex-containing devices with a negative latex skin test but a positive sIgE were also included. CRD was performed with the ImmunoCAP ISAC microarray and traditional singleplexed ImmunoCAP. RESULTS: In all patients, the diagnosis of latex allergy could be established by the combination of recombinant latex components present on the microarray (Hev b 1, Hev b 3, Hev b 5 and Hev b 6.02). Over three-quarters of our patients were sensitized for Hev b 5 and/or Hev b 6.02. Some patients also displayed reactivity for Hev b 1 and/or Hev b 3. In contrast, none of the individuals sensitized to natural rubber latex or control individuals demonstrated IgE reactivity for rHev b 1, rHev b 3, rHev b 5 or rHev b 6.02. Three-quarters of the patients sensitized to latex displayed a positive microarray result for recombinant latex profilin (rHev b 8). In contrast to the results obtained by traditional ImmunoCAP for bromelain, almost no sensitization for cross-reactive carbohydrates was demonstrated by bromelain spotted on the microarray. CRD by traditional singleplexed ImmunoCAP showed highly comparable results. CONCLUSION: CRD by microarray is a reliable tool for diagnosing latex allergy. In addition, the technique allows discrimination between genuine allergy and sensitization. CRD by microarray can improve the diagnosis of IgE-mediated latex allergy by discriminating between genuine allergy and sensitization. CRD by microarray is a reliable tool to diagnose latex allergy. In addition, the technique allows discrimination between a genuine allergy and simple sensitization.

Interference of cross-reactive carbohydrates in the determination of specific IgE in alcohol drinkers and strategies to minimize it: the example of latex.

BACKGROUND: Cross-reactive carbohydrate determinants (CCDs) are N-glycans in plant and invertebrate proteins that interfere with specific IgE determinations. The prevalence of IgE to Man2XylFucGlcNAc2 (MUXF), the CCD from bromelain, may be increased in heavy drinkers. OBJECTIVE: To further investigate the relationship of alcohol consumption to CCD specific IgE. Latex was used as an example for investigating CCD interference with in vitro allergy testing and how to minimize the interference by using nonglycosylated recombinant allergens and inhibition assays. METHODS: We determined the levels of IgE to CCD markers (MUXF and ascorbate oxidase) and natural rubber latex in 270 adults without a history of latex allergy (73 abstainers or occasional drinkers, 76 light drinkers, 47 moderate drinkers, and 74 heavy drinkers). In cases with latex reactivity, we performed inhibition assays with MUXF and screened for IgE to a panel of recombinant latex allergens. Fourteen-day serologic follow-up was available for a subset of individuals. RESULTS: Moderate to heavy drinkers displayed an increased prevalence of IgE to CCD markers. The presence of CCD specific IgE was closely associated with latex IgE reactivity. Inhibition studies and the absence of reactivity to nonglycosylated recombinant latex allergens indicated CCD interference in latex IgE determinations. Serum levels of specific IgE decreased with alcohol abstention. CONCLUSIONS: In this population, alcohol consumption is associated with an increased prevalence of IgE reactivity to natural rubber latex due to CCD interference. The use of nonglycosylated recombinant allergens and inhibition assays may help to minimize CCD interference in populations in which IgE to CCDs is common.

Immunological and allergenic responses induced by latex fractions of Calotropis procera (Ait.) R.Br.

Immunological and allergenic responses against the latex of Calotropis procera were investigated in mice by oral and subcutaneous routes. The latex was fractionated according to water solubility and molecular size of its components. The fractions were named as non-dialyzable latex (NDL) corresponding to the major latex proteins, dialyzable latex (DL) corresponding to low molecular size substances and rubber latex (RL) which was highly insoluble in water. Anti-sera against these fractions were assayed for total IgG and IgA titration by ELISA and IgE and IgG(1) were quantified by passive cutaneous anaphylaxis (PCA) in rats and mice, respectively. None of the fractions induced antibodies level increases when mice received latex fractions by oral route and thus, did not develop allergy. Nonetheless, anti-sera of mice sensitized with NDL and RL by subcutaneous route displayed considerable immunological response while DL did not. IgG level augmented consistently against NDL and RL while IgA response was detected only to NDL. NDL and RL induced very strong PCA reactions suggesting that both fractions would contain latex substances involved in allergy. Furthermore, protein analysis of NDL and RL suggests that RL still retain residual proteins abundantly found in NDL that could explain its similar allergenic effect. No IgG(1) reaction was detected in any of the anti-sera tested. According to the results, the proteins of latex of Calotropis procera can provoke allergy by subcutaneous route. The NDL has previously shown to display anti-inflammatory and analgesic activities by intraperitoneal injection. It should be relevant to determine whether NDL could induce such activities when assayed by oral route since it was ineffective to induce allergy by this way.

Natural rubber latex and hymenoptera venoms share ImmunoglobinE-epitopes accounting for cross-reactive carbohydrate determinants.

BACKGROUND: Epidemiological data on the prevalence and risk factors of latex sensitization have suggested a significant association between latex sensitization and the presence of one or more positive skin prick test responses to aeroallergens, food allergens and to one or more insect venoms. Xylose and core 3-fucose are typical complex glycans in plants and are foreign to mammals. Plant N-glycans and insect N-glycans may cross-react in humans. OBJECTIVE: The aim of our study was to investigate whether there are cross-reactive IgE-binding structures in natural rubber latex (NRL) and hymenoptera venoms and to examine their nature. METHODS: Hundred and twenty-five consecutive patients with insect venom allergy were screened for coincidental latex-specific IgE. IgE-binding components in the venoms from Apis mellifera and/or vespula species and in NRL extracts were characterized by IgE-immunoblotting to the natural allergen sources and determination of specific IgE to recombinant allergens. Cross-reactive components were investigated by inhibition experiments. The involvement of carbohydrates in the constitution of cross-reactive IgE-epitopes was further examined by specific IgE-binding to cross-reactive carbohydrate determinants (CCD) in bromelain and horseradish peroxidase as well as by periodate treatment. RESULTS: NRL glove extracts inhibited patients' serum IgE-binding to venom allergens. Vice versa, the IgE-binding to latex glove extracts could be inhibited by pre-incubation with the insect venoms. Specific IgE-binding to recombinant latex allergens was absent, whereas the cross-reactive IgE-epitopes were sensitive to periodate treatment and specific IgE to CCD (MMXF and MUXF type) could be detected. CONCLUSION: Insect venoms and NRL share IgE-binding CCD that may be responsible for positive serological test results to NRL in patients with insect venom allergy. This copositivity occurs frequently (13.6%) among venom-allergic individuals and did not elicit clinical symptoms upon contact to latex in the patients examined. In contrast, true cosensitization to insect venoms and NRL allergens can occur and may not be missed.

A major allergen from pollen defines a novel family of plant proteins and shows intra- and interspecies [correction of interspecie] cross-reactivity.

Olive tree (Olea europaea) pollen is a main cause of allergy associated with extensive areas of Europe and North America. Ole e 10, a small (10.8 kDa) and acidic (pI 5.8) protein, has been identified as a major allergen from the olive pollen, isolated, and characterized. Circular dichroism analysis gave 17% alpha helix, 33% beta sheet, and 21% beta turn for its secondary structure. Based on amino acid sequences of tryptic peptides, the protein was cloned and sequenced. The allergen consists of a single polypeptide chain of 102 aa, with a signal peptide of 21 residues. Ole e 10 showed homology with the C-terminal domain of another olive allergen, Ole e 9 (1,3-beta-glucanase, 53% identity), with deduced sequences from Arabidopsis thaliana genes (42-46% identity) and with polypeptide segments (Cys boxes) of proteins involved in yeast development (Epd1/Gas-1p/Phr2 families; 42-43% similarity). Ole e 10 showed 55% prevalence for olive-allergic patients and exhibited an IgE response dependent on its conformation. Remarkable IgE cross-reactivity was detected with Ole e 9, but no correlation was observed between the individual IgE responses to both allergens. Ole e 10 shares IgE B cell epitopes with proteins from Oleaceae, Gramineae, Betulaceae, Chenopodiaceae, Cupressaceae, Ambrosia, and Parietaria pollens, latex, and vegetable foods, such as tomato, kiwi, potato, and peach. These data indicate that Ole e 10 is a new pan-allergenic plant protein that shows notable intra- and interspecie IgE cross-reactivity and is a powerful candidate to be involved in pollen-latex-fruit syndrome.

Engineered allergens for immunotherapy.

PURPOSE OF REVIEW: Specific immunotherapy is a clinically effective causative treatment for allergic conditions. However, the reagents used for immunotherapy are crude extracts prepared from natural sources with potential life-threatening anaphylactic side effects. Molecular cloning of allergens has made it feasible to design novel therapeutic approaches for improved and safer forms of allergen-specific immunotherapy. The purpose of this review is to examine recent advances made in the last 2 years in genetic engineering of allergens for specific immunotherapy. RECENT FINDINGS: Genetic engineering of allergen with nil or low IgE reactivity but retained T-cell reactivity offers a novel therapeutic approach to improving safety and efficacy of allergen-specific immunotherapy. Hypoallergenic forms of major allergens have been produced, with reduced IgE epitopes while preserving other characteristics of the molecule to induce a protective response. SUMMARY: Hypoallergenic forms of major allergens are potential candidates for allergen-specific immunotherapy in the future. These genetically engineered hypoallergens now need to be tested in clinical trials before being widely used. Safer and more efficacious vaccines would increase patient compliance leading to extensive use of immunotherapy.

Listening to mozart reduces allergic skin wheal responses and in vitro allergen-specific IgE production in atopic dermatitis patients with latex allergy.

In atopic dermatitis patients with latex allergy, listening to Mozart reduced skin wheal responses induced by latex, but not by histamine, whereas listening to Beethoven failed to produce similar results. Listening to Mozart also decreased in vitro total IgE and latex-specific IgE production with concomitant skewing of the cytokine pattern toward the Th1 type, that is, an increase in Th1 cytokine production and decrease in Th2 cytokine production by peripheral blood mononuclear cells, whereas listening to Beethoven failed to do so. These results suggest that therapy using specific types of music may be an effective treatment of allergic diseases.

Tomato allergy in children and young adults: cross-reactivity with latex and potato.

BACKGROUND: Several studies have shown that allergy to natural rubber latex is associated with cross-reactivity to certain foods such as tomato and potato. The objective was to investigate the clinical and immunologic differences between a group of patients with clinical allergy to tomato and latex and another which had only clinical allergy to tomato. We also aimed to assess, in vitro, the relationship of tomato and latex allergens, which could explain the cross-reactivity. METHODS: Forty patients with histories of adverse reactions to tomato and IgE-mediated hypersensitivity were enrolled in the study. Tomato, latex, and potato components were analyzed by SDS-PAGE immunoblotting. CAP and immunoblot inhibition were used to study allergen cross-reactivity. RESULTS: Patients from group A had a mean age of 13.2 years, and in group B the mean age was 21.7 years. In group B, 9/10 patients belonged to the latex-fruits syndrome. All patients of both groups tolerated potato. Immunoblotting patterns obtained with patients' sera from pool A showed IgE-binding bands to tomato ranging from 44 to 46 kDa and a triple band at 67 kDa. For latex, there was a strong binding at 44 kDa, and potato showed a strong band of 44 kDa and a 67-kDa triple band. In pool B, the binding to the band of 44 kDa in latex and tomato was more intense than in pool A. In pool A, immunoblot inhibition with potato allergen showed an intense inhibition of the three allergens (potato, latex, and tomato); with latex, inhibition was partial and with tomato, a complete inhibition of tomato and latex was observed, and a partial inhibition of potato. In pool B, the inhibition pattern followed a similar tendency to pool A. The CAP inhibition confirmed the high rate of cross-reactivity between tomato, potato, and latex. CONCLUSIONS: In our study, tomato, potato, and latex showed a common band of 44-46 kDa probably corresponding to patatin. This protein could be implicated in the high cross-reactivity between tomato, latex, and potato observed in the immunoblot and CAP inhibition.

Hev b 8, the Hevea brasiliensis latex profilin, is a cross-reactive allergen of latex, plant foods and pollen.

BACKGROUND: Plant profilins are important pan-allergens. They are responsible for a significant percentage of pollen-related allergies. Limited information is available about their involvement in the latex-fruit syndrome and the cross-reactivities between latex and pollen. We aimed to clone and express the Hevea brasiliensis latex profilin to investigate its allergological significance and serological cross-reactivities to profilins from plant foods and pollens. METHODS: A DNA complementary to messenger RNA (cDNA) coding for the Hevea latex profilin, Hev b 8, was amplified by polymerase chain reaction from latex RNA. Recombinant (r)Hev b 8 was produced in Escherichia coli and used to screen sera from 50 latex- allergic health care workers (HCWs) with well-documented histories of food and pollen allergy and 34 latex-allergic spina bifida (SB) patients. The cross-reactivity of natural Hev b 8 and rHev b 8 with other plant profilins was determined by ELISA inhibition assays. A three-dimensional homology model of Hev b 8 was constructed based on known profilin structures. RESULTS: The cDNA of Hev b 8 encoded a protein of 131 amino acids with a predicted molecular mass of 14 kD. Twelve of the 50 HCWs and 2 of the 34 SB patients were sensitized to Hev b 8. All Hev b 8-sensitized patients showed allergic symptoms to pollen or plant foods. Cross-reactivities between profilins of latex, pollen and plant food were illustrated by their ability to inhibit IgE binding to rHev b 8. Homology modeling of Hev b 8 yielded a structure highly similar to Bet v 2, the birch pollen profilin, with the most distinct differences located at the N-terminus. CONCLUSIONS: We conclude that primary sensitization to latex profilin in the majority of cases takes place via pollen or food profilins. Additionally, pollinosis and food-allergic patients with profilin-specific IgE can be at risk of developing latex allergy.