Lipid Transfer Protein Sensitization Research Articles

Understanding of lipid transfer protein sensitization patterns and its clinical significance in children.

Background: Lipid transfer proteins (LTP) are the most common food allergens in the Mediterranean region. Objective: The study aimed to investigate co-sensitization patterns and cluster relationships between LTP allergen molecules across a broad range of allergen-specific sensitization patterns, and clinical outcomes in eastern Mediterranean children. Methods: Among 496 children evaluated for multiple sensitizations with multiplex testing, 105 children (21%) with 16 different LTP sensitizations were analyzed. Clinical reactivity was examined based on clear-cut history of immunoglobulin E mediated symptoms (oral allergy syndrome [OAS], systemic reactions, and anaphylaxis). Results: All children included were sensitive to food LTPs, but 56% were sensitive to pollen LTPs. The number of children with OAS and clinical reactivity was 12 and 59, respectively, and no cofactors were reported. The most common sensitizations were Pru p 3 (74%) and Cor a 8 (66%). Significant correlations were observed in the heatmap between the LTP molecules other than Par j 2 and Tri a 14. Overall, clinical reactivity was associated with increased age and number of LTP molecule positivity. Conclusion: In the eastern Mediterranean region, 21% of children with multiple food and/or pollen sensitizations were found to have LTP sensitization; however, almost half reported clinical reactivity. The hierarchical pathway highlights that distinct LTP allergen molecules can act as primary sensitizers. Clinical reactivity is linked to increasing numbers of LTP molecule positivity and increasing age.

Occupational hops allergy with nonspecific lipid transfer protein sensitization: Cross-reactivity with food nonspecific lipid transfer protein

Occupational hops allergy with nonspecific lipid transfer protein sensitization: Cross-reactivity with food nonspecific lipid transfer protein

Differences in Linear Epitopes of Ara h 9 Recognition in Peanut Allergic and Tolerant, Peach Allergic Patients.

BackgroundPeanut-allergic patients from the Mediterranean region are predominantly sensitized to the lipid transfer protein (LTP) Ara h 9, and the peach LTP Pru p 3 seems to be the primary sensitizer. However, LTP sensitization in peanut allergy is not a predictive marker for clinically relevant symptoms.ObjectiveWe aimed to identify sequential epitopes of IgE and IgG4 from Pru p 3 and Ara h 9 in peach-allergic patients sensitized to peanuts. We also sought to determine the differences in IgE and IgG4 binding between patients who had developed peanut allergy and those tolerating peanuts.MethodsA total of 46 peach-allergic patients sensitized to peanuts were selected. A total of 35 patients were allergic to peanuts (peanut-allergic group) and 11 were tolerant to peanuts (peanut-tolerant group). We measured sIgE and sIgG4 in peanut, peach, and their recombinant allergen (Ara h 1, Ara h 2, Ara h 3, Ara h 8, and Ara h 9) with fluorescence enzyme immunoassay. We examined the IgE and IgG4 binding to sequential epitopes using a peptide microarray corresponding to linear sequences of the LTPs Ara h 9 and Pru p 3 with a library of overlapping peptides with a length of 20 amino acids (aa) and an offset of 3 aa.ResultsThe frequency and the intensity of IgE recognition of Ara h 9 and Pru p 3 peptides were higher in the peanut-tolerant group than in the peanut-allergic group. We found four Ara h 9 peptides (p4, p14, p21, and p25) and four Pru p 3 peptides (p1, p3, p21, and p24) with a significantly elevated IgE recognition in peanut-tolerant patients. Only one peptide of Ara h 9 (p4) recognized by IgG4 was significantly elevated in the peanut-tolerant group. The IgG4/IgE ratio of Ara h 9 peptide 4 was significantly higher in peanut-tolerant patients than in peanut-allergic patients, while no significant differences were observed in the IgG4/IgE ratio of this peptide in Pru p 3.ConclusionAlthough we found significant differences in IgE and IgG4 recognition of Ara h 9 and Pru p 3 between peanut-tolerant and peanut-allergic patients (all of whom were allergic to peach), polyclonal IgE peptide recognition of both LTPs was observed in peach-allergic patients tolerating peanuts. However, the IgG4 blocking antibodies against Ara h 9 peptide 4 could provide an explanation for the absence of clinical reactivity in peanut-tolerant peach-allergic patients. Further studies are needed to validate the usefulness of IgG4 antibodies against Ara h 9 peptide 4 for peanut allergy diagnosis.

Peanut allergy in Italy: Aunique Italian perspective.

Peanut allergy has not been well characterized in Italy. Our aim was to better define the clinical features of peanut allergy in Italy and to detect the peanut proteins involved in allergic reactions. A total of 22 centers participated in a prospective survey of peanut allergy over a 6-month period. Clinical histories were confirmed by invivo and/or in vitro diagnosticmeans in all cases. Potential risk factors for peanutallergy occurrence were considered. Levels of IgE to Arachis hypogea (Ara h) 1, 2, 3, 6, 8, and 9 and profilin were measured. A total of 395 patients (aged 2-80 years) were enrolled. Of the participants, 35% reported local reactions, 38.2% reported systemic reactions, and 26.6% experienced anaphylaxis. The sensitization profile was dominated by Ara h 9 (77% of patients were sensitized to it), whereas 35% were sensitized to pathogenesis-related protein 10 (PR-10) and 26% were sensitized to seed storage proteins (SSPs). Sensitization to 2S albumins (Ara h 2 and Ara h 6) or lipid transfer protein (LTP) was associated with the occurrence of more severe symptoms, whereas profilin and PR-10 sensitization were associated with milder symptoms. Cosensitization to profilin reduced the risk of severe reactions in both Ara h 2- and LTP-sensitized patients. SSP sensitization prevailed in younger patients whereas LTP prevailed in older patients (P<.01). SSP sensitization occurred mainly in northern Italy, whereas LTP sensitization prevailed in Italy's center and south. Atopic dermatitis, frequency of peanut ingestion, peanut consumption by other family members, or use of peanut butter did not seem to be risk factors for peanut allergy onset. In Italy, peanut allergy is rare and dominated by LTP in the country's center and south and by SSP in the north. These 2 sensitizations seem mutually exclusive. The picture differs from that in Anglo-Saxon countries.

Lipid Transfer Protein Sensitization: Risk of Anaphylaxis and Molecular Sensitization Profile in Pru p 3-Sensitized Patients

Background: Component-resolved diagnosis reveals the IgE response to many inhaled, food, and other allergens, improving the understanding and diagnosis of allergic diseases. Objective: The aims of the study are to study the recognition of different lipid transfer proteins (LTPs) and other allergen families in a large group of people sensitized to Pru p 3 and to analyze the relationship between the clinical entities and the allergens. Methods: This cross-sectional study included a large cohort of patients with positive skin tests to peach fruit and Pru p 3 specific IgE antibodies. Respiratory and food allergy symptoms were collected, and we performed prick tests with pollen, plant food, and other allergens plus the ImmunoCAP ISAC assay. Results: Our sample consisted of 421 people with a mean age of 33.25 years (range 16–68); 54.6% were women. Clinical entities included anaphylaxis (37.1%), urticaria (67.9%), and oral allergy syndrome (59.1%). Rhinitis, rhinoconjunctivitis, and/or asthma were diagnosed in 71.8% of the participants. The most pronounced correlation existed between sensitization to Pru p 3 and to Jug r 3, Pla a 3, Ara h 9, and Cor a 8. We found a higher incidence of anaphylaxis in people with 5 or more recognized LTPs. No association was observed between inhaled and food allergies. Conclusion: Most Pru p 3-sensitized participants were sensitized to additional allergens from the same family and, to a lesser extent, to other allergens, mainly in the profilin and PR-10 protein families. Anaphylaxis occurred in more than a third of the cases evaluated, and almost three-quarters of them had respiratory symptoms. Respiratory and food allergies involving LTPs do not seem to be associated.

Walnut Allergy Across Europe: Distribution of Allergen Sensitization Patterns and Prediction of Severity

Walnut allergy is common across the globe, but data on the involvement of individual walnut components are scarce. To identify geographical differences in walnut component sensitization across Europe, explore cosensitization and cross-reactivity, and assess associations of clinical and serological determinants with severity of walnut allergy. As part of the EuroPrevall outpatient surveys in 12 European cities, standardized clinical evaluation was conducted in 531 individuals reporting symptoms to walnut, with sensitization to all known walnut components assessed in 202 subjects. Multivariable Lasso regression was applied to investigate predictors for walnut allergy severity. Birch-pollen-related walnut sensitization (Jug r 5) dominated in Northern and Central Europe and lipid transfer protein sensitization (Jug r 3) in Southern Europe. Profilin sensitization (Jug r 7) was prominent throughout Europe. Sensitization to storage proteins (Jug r 1, 2, 4, and 6) was detected in up to 10% of subjects. The walnut components that showed strong correlations with pollen and other foods differed between centers. The combination of determinants best predicting walnut allergy severity were symptoms upon skin contact with walnut, atopic dermatitis (ever), family history of atopic disease, mugwort pollen allergy, sensitization to cat or dog, positive skin prick test result to walnut, and IgE to Jug r 1, 5, 7, or carbohydrate determinants (area under the curve= 0.81; 95% CI, 0.73-0.89). Walnut-allergic subjects across Europe show clear geographical differences in walnut component sensitization and cosensitization patterns. A predictive model combining results from component-based serology testing with results from extract-based testing and information on clinical background allows for good discrimination between mild to moderate and severe walnut allergy.

Lipid Transfer Protein allergy in the United Kingdom: Characterization and comparison with a matched Italian cohort.

BackgroundAlthough pollen‐related food allergy occurs in all European populations, lipid transfer protein (LTP) allergy is considered to manifest mainly in Mediterranean countries. We aimed to characterize adults presenting with LTP allergy in a northern European country.MethodThe clinical history and sensitization patterns of subjects born and residing in the United Kingdom (UK), with a prior diagnosis of LTP allergy and sensitization to the peach LTP allergen Pru p 3, were compared to UK subjects with pollen food syndrome (PFS). The sensitization patterns were also evaluated against a matched cohort of Italian subjects diagnosed with LTP allergy.ResultsNone of the 15 UK PFS subjects had a positive SPT to LTP‐enriched peach reagent, compared to 91% of the 35 UK LTP subjects. The UK LTP cohort were also more likely to have positive skin prick tests to cabbage, lettuce and mustard and sensitization to the LTP allergens in peach, walnut, mugwort and plane tree These sensitization patterns to individual allergens were not significantly different to those obtained from the Italian LTP subjects, with significant correlations between Pru p 3 and the LTP allergens in peanuts, walnuts, plane tree and mugwort in both groups.ConclusionNative UK subjects with LTP allergy are not dissimilar to those with LTP allergy in southern Europe. Testing to LTP‐enriched peach SPT reagent and/or LTP allergens in peach, walnut, mugwort and plane tree may enhance diagnostic accuracy.

Mugwort Pollen-Related Food Allergy: Lipid Transfer Protein Sensitization and Correlation With the Severity of Allergic Reactions in a Chinese Population.

PurposeLittle is known about the importance of lipid transfer protein (LTP) sensitization in China. In this study, we investigated the relationship between LTP sensitization and the severity of clinical symptoms in a population of patients with mugwort pollen-related food allergy.MethodsFood-induced symptoms were evaluated in 148 patients with mugwort pollen allergy by a standardized questionnaire. Specific immunoglobulin E (IgE) to Art v 1, Art v 3, Pru p 3, Ara h 9 and Cor a 8 were quantified by ImmunoCAP. Immunoblotting of peach extracts were performed with sera from peach-allergic patients.ResultsIn total, 72% (107/148) of the study population experienced food allergy. Forty-eight percent (51/107) of patients with mugwort pollen-related food allergy experienced at least 1 episode of food-induced anaphylaxis. Food allergy correlated with IgE reactivity to Art v 3, but not to Art v 1. Sensitization to Pru p 3, Ara h 9 or Cor a 8 was prevalent (80%, 69 or 63%, respectively) among individuals with food allergy. Food allergic patients with systemic reactions (SR) had higher values for Pru p 3, Ara h 9 and Cor a 8 than patients with oral allergy syndrome (OAS). Furthermore, the strong IgE reactivity detected in immunoblots of peach extracts indicated that Pru p 3 was the major allergen and was more prevalent in patients with SR than in patients with OAS (100% vs. 55%).ConclusionsLTPs are major food allergens for mugwort pollen-related food allergy in China, and may contribute to SR.

The clinical relevance of lipid transfer protein.

Despite a huge number of studies, many aspects of the lipid transfer protein (LTP) syndrome, the most frequent primary food allergy in Mediterranean countries, remain unclear. Its peculiar geographical distribution, along with the extreme variability of its clinical expression, makes this type of food allergy something unique in the panorama of IgE-mediated food-induced allergic reactions. This review article tried to summarize the current knowledge about the most important aspects of LTP sensitization and allergy, along with the importance of positive and negative co-factors in the clinical expression of the syndrome as well as the issues regarding the cross-reactivity between LTPs present in botanically related and unrelated foods. Further, the possible absence of the protein from some plant foods is discussed.

Pru p 3, a marker allergen for lipid transfer protein sensitization also in Central Europe.

In the Mediterranean area, lipid transfer proteins (LTPs) are important causes of plant‐food allergies often associated with severe allergic reactions. There, peach LTP (Pru p 3) seems to be the primary sensitizer, whereas in Central Europe, little is known about the importance of LTP sensitization. In this region, allergen extract‐based diagnosis is often complicated by co‐sensitization to Bet v 1, the major birch pollen allergen, its cross‐reactive food allergens, and profilins. We investigated the role of LTP sensitization in Central European patients displaying strong allergic reactions to plant‐derived food. Analysis of IgE reactivity revealed that ten of thirteen patients were sensitized to Pru p 3, nine to Bet v 1, and two to profilin. Our results showed that LTP sensitization represents a risk factor for severe allergic symptoms in Central Europe. Furthermore, the strong IgE reactivity detected in immunoblots of plant‐food extracts indicated that Pru p 3 can be used as a marker allergen for LTP sensitization also in Central European patients.

Differential diagnosis of LTP‐sensitised patients in Central Europe

Lipid transfer protein (LTP) is a major allergen in peach often causing anaphylactic reactions with a high prevalence of sensitization in the Mediterranean area. The prevalence of LTP sensitization in Central Europe is currently unknown, where the diagnosis is complicated by a high background sensitization to the major birch pollen allergen, Bet v 1, and Bet v 1 cross-reactive food allergens, which cause only mild reactions. LTP and Bet v 1-related proteins are both distributed throughout the plant-kingdom. In this study, we aimed to characterize the sensitization-patterns of patients with severe reactions to plant-derived food in Austria. Thirteen patients reporting strong reactions after consumption of fruits, vegetables or herbs were invited to skin prick and prick to prick tests. For visualizing patients' IgE-reactivity patterns, immunoblots were performed, which allowed the determination of specific IgE to raw and boiled parsley, raspberry, apricot, and peach. These immunoblots showed that cooking did not influence IgE binding to LTPs, while cooking reduced IgE binding to all Bet v 1-related proteins. We further observed that LTP-sensitized patients showed variable IgE reactivity to different LTPs, however, the strongest reactions were seen to fruits from the Rosaceae family, especially to peach, suggesting that peach LTP (Pru p 3) contains the majority of IgE epitopes also for a Central European population. Analysis of IgE reactivity to single molecules (including Bet v 1 and Pru p 3) using an allergen micro-array (ISAC) and single ImmunoCAP measurements enabled to determine the following sensitization patterns: 1 patient was monosensitized to Bet v 1, 3 were monosensitized to LTP, whereas 8 showed a co-sensitization to Bet v 1 and LTP and 1 patient was monosensitized to profilin. Based on this study, we conclude that analysis of specific IgE to the LTP Pru p 3 from peach is also sufficient for diagnosis of reactions to Rosacea fruits even in regions where frequent co-sensitization to Bet v 1 makes the interpretation of extracts-based skin prick tests difficult. In addition, also other plant-related panallergens, such as profilin, should be included in such a differential diagnostic workup scheme.

High prevalence of lipid transfer protein sensitization in apple allergic patients with systemic symptoms.

BackgroundApple allergy manifests as two main groups of clinical entities reflecting different patterns of allergen sensitization: oral allergy syndrome (OAS) and generalized symptoms (GS).ObjectiveWe analysed the sensitization profile to a wide panel of different components of food allergens (rMal d 1, Mal d 2, rMal d 3, rMal d 4, rPru p 3, rBet v 1 and Pho d 2) for a population of Mediterranean patients with OAS and GS to apple.MethodsPatients (N = 81) with a history of apple allergy that could be confirmed by positive prick-prick test and/or double-blind-placebo-controlled food challenge (DBPCFC), were included. Skin prick test (SPT) and ELISA were performed using a panel of inhalant, fruit and nut allergens. ELISA and ELISA inhibition studies were performed in order to analyse the sensitization patterns.ResultsThirty-five cases (43.2%) had OAS and 46 (56.8%) GS. SPT showed a significantly higher number of positive results with peach, cherry and hazelnut in those with GS. ELISA showed a significantly high percentage of positive cases to rMal d 3, rMal d 4, rPru p 3 and Pho d 2 in patients with OAS and GS compared to controls, and to rBet v 1 in patients with OAS vs controls and between OAS and GS patients. Three different patterns of recognition were detected: positive to LTP (rMal d 3 or rPru p 3), positive to profilin (rMal d 4 and Pho d 2), or positive to both. There were also patients with rMal d 1 recognition who showed cross-reactivity to rBet v 1.ConclusionIn an apple allergy population with a high incidence of pollinosis different patterns of sensitization may occur. LTP is most often involved in those with GS. Profilin, though more prevalent in patients with OAS, has been shown to sensitise patients with both types of symptoms.

In vivo and in vitro techniques in the diagnosis of lipid transfer protein sensitization

In vivo and in vitro techniques in the diagnosis of lipid transfer protein sensitization

Anaphylaxis to plant-foods and pollen allergens in patients with lipid transfer protein syndrome

Nonspecific lipid transfer protein (LTP) is the main cause of primary food allergy in adults living in the Mediterranean area. The way allergic patients get sensitized to this protein is all but established, and the clinical expression of sensitization is extremely variable, ranging from long-lasting symptomless sensitization to severe anaphylaxis. Such variability is seemingly due to the presence/absence of a number of cofactors. The possibility that LTP sensitization occurs via the inhalation of LTP-containing pollen particles seems unlikely; in contrast, peach particles containing the protein seem able to sensitize both via the airways and the skin. Cosensitization to pollen allergens as well as to labile plant food allergens makes LTP allergy syndrome less severe. In some LTP sensitized subjects clinical food allergy occurs only in the presence of cofactors such as exercise, NSAIDs, or chronic urticaria. Lipid transfer protein allergy syndrome shows some peculiarities that are unique in the primary food allergy panorama: geographical distribution, frequent asymptomatic sensitization, frequent need for cofactors, and reduced severity when pollen allergy is present. Future studies will have to address these points as the results may have favorable effects on other, more severe, types of food allergy.

Diagnostic usefulness of component-resolved diagnosis by skin prick tests and specific IgE to single allergen components in children with allergy to fruits and vegetables

IntroductionThe accurate identification of sensitizing proteins in patients allergic to plant-derived foods is extremely important, allowing a correct dietary advice. We aimed to evaluate the diagnostic usefulness of skin prick tests (SPT) and specific IgE (sIgE) with single molecular allergen components in children with allergy to fruits and vegetables. MethodsTwenty children underwent SPT with a palm profilin (Pho d 2, 50μg/mL); a Mal d 1-enriched apple extract (2μg/mL) (PR-10 allergen); and a peach Lipid Transfer Protein (LTP) (Pru p 3, 30μg/mL). Detection of sIgE to rBet v 1, rBet v 2, Phl p 12 and Pru p 3 was also measured. ResultsAllergy to multiple fruits and vegetables was observed in 11 (55%) children. Sensitization by SPT to Pho d 2, Mal d 1, and Pru p 3 occurred in 5, 7, and 8 cases, respectively. LTP sensitization appeared to be associated with peach allergy but not with severe reactions, and profilins sensitization to melon and tomato allergy. Kiwi sensitization (12 cases), the plant-derived food that caused more allergic reactions, seemed mostly species-specific. The concordance of SPT extracts and sIgE to the corresponding pan-allergens was high for profilins (k=0.857) and LTP (k=0.706), while for PR-10 allergens it was absent (k=0.079). ConclusionsPan-allergen sensitization in children with allergy to fruits and vegetables was common and often multiple. There was no association of severe reactions to LTP sensitization. The introduction of routine SPT to pan-allergens can be a simple and feasible way of improving diagnostic and therapeutic efficacy.

Peach-Induced Contact Urticaria Is Associated with Lipid Transfer Protein Sensitization

Background: Peach-induced contact urticaria is frequent in peach-allergic subjects. Objective: It was the aim of this study to detect whether contact urticaria is associated with a specific peach allergen. Methods: Ninety-two peach-allergic subjects were studied. Patients were diagnosed as being sensitized to lipid transfer protein (LTP; Pru p 3) or as having a pollen-food allergy syndrome induced by Pru p 1 and/or profilin, Pru p 4, on the basis of the results of a skin prick test containing these allergenic proteins in an isolated form. Specific IgE to peach extract was measured as well. Contact urticaria was confirmed by a contact test with intact, untreated peach. A contact test with nectarine was carried out as control. Results: Overall, contact urticaria was present in 21% of patients; the peach contact test scored positive in all cases. Contact urticaria was significantly more frequent in patients hypersensitive to LTP (63%) than in subjects with pollen-food allergy syndrome (6%; p < 0.001) and was not associated with a higher level of peach-specific IgE. In several cases, contact urticaria preceded the onset of food allergy by years. The contact test with nectarine scored negative in 5/5 cases. Conclusions: Although the peach contact test was not performed in all subjects, and peach allergy was not confirmed by oral challenges, this study shows that peach-induced contact urticaria is associated with sensitization to peach LTP. The negative clinical history and contact test with nectarine along with the well-known high concentration of LTP in peach fuzz suggest that peach fuzz plays a role in the pathogenesis of contact urticaria.

Lipid transfer protein–linked hazelnut allergy in children from a non-Mediterranean birch-endemic area

Hazelnut allergy in birch pollen-exposed areas is usually due to cross-reactivity (Cor a 1 and 2) and is usually mild in nature (oral allergy). In areas without birches, severe reactions are more prevalent and linked to sensitization to the lipid transfer protein (LTP) Cor a 8. We sought to investigate whether sensitization to LTP plays a role in more severe (objective) hazelnut-induced symptoms in children from a birch-endemic area. Sensitization to Cor a 8, Cor a 2, Cor a 1, and Bet v 1 was determined by means of RASTs and immunoblotting in hazelnut-sensitized children with (n = 8) and without (n = 18) objective reactions during double-blind, placebo-controlled food challenges. Additionally, samples from 191 hazelnut-sensitized nonchallenged children were analyzed. Children with objective reactions during double-blind, placebo-controlled food challenge had higher IgE titers to hazelnut (P < .001) and recognized more allergens on immunoblotting (P = .001) than those without such reactions. All children with objective symptoms were sensitized to Cor a 8 (0.51-23.3 IU/mL) compared with only 1 child without objective reactions (0.90 IU/mL). In a multivariate analysis only IgE against Cor a 8 remained as an independent risk factor (undefined odds ratio; P < .0001). In the group of nonchallenged children (n = 191), the prevalence of LTP sensitization was greater than 30%. Unexpectedly, sensitization to Cor a 1 was observed in children not sensitized to Bet v 1. Sensitization to hazelnut LTP is a risk factor for objective symptoms in children from a birch-endemic area.

Lipid transfer protein allergy: primary food allergy or pollen/food syndrome in some cases

To summarize recent findings on non-specific lipid transfer proteins in food allergy, with a specific focus on the localization, stability and route of sensitization. Plant non-specific lipid transfer proteins are major food allergens, especially in the Mediterranean area. They have been identified as allergens in a number of foods and the list grows ever longer. As non-specific lipid transfer proteins are considered to be "true" food allergens that sensitize directly via the gastrointestinal tract their stability during food processing and gastric digestion has been studied in more detail. In addition, several groups have tried to determine the sensitization patterns of lipid transfer protein-reactive patients, to determine and possibly clarify the observed geographical differences in sensitization. Different sensitization routes (via the respiratory tract or even transdermally) have been suggested. As the structure and molecular properties of non-specific lipid transfer proteins are resolved and more purified non-specific lipid transfer proteins become available for diagnostic purposes, detailed studies on the sensitization pattern and route are becoming feasible. Continuing studies on the pattern of lipid transfer protein sensitization will give more insight into the development and possible treatment of lipid transfer protein-related food allergy.