Síndrome LTP: Caraterização do perfil clínico e molecular de sensibilização – Método Alex® Macroarray

Introdução: A alergia alimentar afeta milhões de pessoas globalmente. As proteínas de transferência lipídica (LTP) são panalergénios presentes em alimentos vegetais cujos sintomas de sensibilização variam de síndrome de alergia oral (SAO) a anafilaxia. Objetivo: Caraterização do perfil de sensibilização clínica e molecular de doentes com história de reação prévia a alimentos contendo LTP. Material e métodos: Estudo retrospetivo incluindo 15 doentes com história de reação sistémica a alimentos contendo LTP. Os doentes foram caracterizados quanto a sintomas e sensibilização em testes cutâneos por picada (TCP) com extrato comercial e alimentos em natureza (TC PP). Foi realizado Macroarray Allergy Explorer-ALEX® para avaliação de valores de IgE total, IgE específica para componentes moleculares (IgEcm) e extratos totais (IgEet). Resultados: Quinze doentes, 73% mulheres, média de idades 30,7±13,7 anos. Média de idades no primeiro episódio foi 21,8±10,5 anos, manifestando-se como anafilaxia n=8 (maçã, pêssego, frutos secos), urticária/angioedema n=4 (maçã, pêssego, amendoim) e SAO n=3 (maçã, pêssego, amendoim). IgE total média: 430,5kU/L. Identificaram-se as seguintes LTP (N; IgEcm média±desvio padrão-kU/L): Pru p 3 (15; 15,7±21,5), Ara h 9 (10; 2,9±4), Mal d 3 (9; 1,5±1,7), Act d 10 (6; 0,6±1), Vit v 1 (6; 1,8±2,5), Cor a 8 (4; 0,1±0,2), Sola l 6 (1; 0,88). Com pêssego todas as associações entre clínica, testes cutâneos e valores de IgE tiveram concordância k=1; concordância da clínica com TCP e TC PP foi superior para maçã (k=0,44; p=0,03); concordância da clínica com IgEet foi superior para amendoim (k=0,87; p<0,01); concordância da clínica com IgEcm foi superior para avelã (k=0,70; p<0,01) e uva (k=0,55; p=0,02). Conclusões: A técnica ALEX® permitiu identificar simultaneamente a IgE total, IgEet e IgEcm, simplificando a interpretação e correlação clínica dos resultados. Neste estudo demonstramos que, para diferentes alimentos, o método diagnóstico com maior concordância com a clínica é variável e dependente do alimento. Será necessário um estudo prospetivo mais alargado para aferir a sensibilidade e especificidade deste teste.

Subjects develop tolerance to Pru p 3 but respiratory allergy to Pru p 9: A large study group from a peach exposed population

Peach tree allergens are present in fruit, pollen, branches, and leaves, and can induce systemic, respiratory, cutaneous, and gastrointestinal symptoms. We studied the capacity of peach fruit/Pru p 1, Pru p 3, Pru p 4, Pru p 7 and peach pollen/Pru p 9 for inducing symptoms following oral or respiratory exposure in a large group of subjects. We included 716 adults (aged 21 to 83 y.o.) exposed to peach tree pollen and fruit intake in the study population. Participants completed a questionnaire and were skin tested with a panel of inhalant and food allergens, including peach tree pollen, Pru p 9 and peach fruit skin extract. Immunoglobulin E antibodies (SIgE) to Pru p 1, Pru p 3, Pru p 4 and Pru p 7 were quantified. Sensitised subjects underwent oral food challenge with peach fruit and nasal provocation test with peach tree pollen and Pru p 9. The prevalence of sensitisation to peach fruit was 5% and most of these had SIgE to Pru p 3, with a very low proportion to Pru p 4 SIgE and no SIgE to Pru p 1 and Pru p 7. In only 1.8%, anaphylaxis was the clinical entity induced. Cases with positive skin tests to peach and SIgE to Pru p 3 presented a good tolerance after oral challenge with peach fruit. The prevalence of skin sensitisation to peach tree pollen was 22%, with almost half recognising Pru p 9. This induced respiratory symptoms in those evaluated by nasal provocation. In a large population group exposed to peach fruit and peach tree pollen, most individuals were tolerant, even in those with SIgE to Pru p 3. A positive response to Pru p 9 was associated with respiratory allergy.

Allergy to Gibberellin-Regulated Proteins (Peamaclein) in Children

<b><i>Background:</i></b> Gibberellin-regulated proteins (GRPs, Peamaclein) are allergens recently identified in plant-derived food allergy (FA), and little is known about the clinical manifestations of this allergic condition in the European population, especially in children. <b><i>Objective:</i></b> Our study aimed to identify and characterize pediatric patients with pollen-FA due to GRP sensitization. <b><i>Methods:</i></b> We retrospectively analyzed the charts of patients referred to the Allergy Unit of the Meyer Children’s Hospital in Florence for suspected FA. Three main eligibility criteria based on the actual knowledge of GRP allergy were used to select patients deserving further investigations: (1) systemic reactions after consumption of fruit or an unknown culprit food, (2) positive skin prick tests to both cypress pollen and Pru p 3-enriched peach peel extracts, (3) negative in vitro test results for Pru p 3 serum-specific Immunoglobulin E (sIgE). We performed the in vitro test to determine the anti-rPru p 7 (Peamaclein) sIgE levels in the selected patients. <b><i>Results:</i></b> We identified 10 pediatric patients with Pru p 7 allergy and described their characteristics. The use of our eligibility criteria showed a high accuracy in identifying these patients: 100% of the selected patients had positive in vitro results for Pru p 7. We therefore proposed a diagnostic algorithm for Pru p 7 allergy. <b><i>Conclusion:</i></b> This is the first case series of European pediatric patients with a demonstrated Peamaclein allergy. These findings broaden our knowledge on GRP allergy in pediatric populations and could help clinicians to suspect, diagnose, and manage this recently discovered plant-derived FA.

A Case Report of Allergy to Peach’s Lipid Transfer Protein

Peach belongs to the Rosaceae family. One of the particularities of this allergy is the difference in clinical reactivity according to geography. We report a 4-year 8-month-old boy with well-controlled asthma and no symptoms of allergic rhinitis, that at the age of 1 year, 15 minutes after the ingestion of a fruit compote, presented urticaria with respiratory discomfort. At the age of 3 years, following ingestion of fruit salad, the child presented a few minutes later, a similar episode but of greater intensity. At the age of 4, following contact with a fruit basket, the child immediately presented a generalized reaction more severe and intense than the previous ones. Investigation of allergies to aerial allergens was negative. Skin tests for cooked and raw peach were positive for the peel and pulp. Specific-IgE was positive for Pru p 3 (5.7 KIU/l) and negative for Pru p 1. LTPs are particularly stable and resistant to proteolysis and heat. Management consisted of avoidance of peach, education of the child and family, and prescription of an emergency kit including self-injectable adrenaline. Our observation highlights the strong association between Pru p 3: peach’s Lipid Transfer Protein (LTP) positivity and the severity of allergy symptoms. We consider this case as a primary sensitization to peach’s LTP.

Pru p 3 Sublingual Immunotherapy in Patients with Lipid Transfer Protein Syndrome: Is It Worth?

<b><i>Background:</i></b> Lipid transfer proteins (LTPs) syndrome is an important cause of multiple plant food allergy in the Mediterranean area. The effectiveness of sublingual immunotherapy (SLIT) with the LTP Pru p 3 extract has been little investigated in the real-world setting. This study aimed to investigate the outcome of Pru p 3 SLIT in real-life patients with LTP syndrome with/without concurrent reactions to peanut and/or nuts. <b><i>Methods:</i></b> This was a prospective real-life study including all patients diagnosed with LTP allergy and treated with Pru p 3 SLIT between 2011 and 2018 in a tertiary hospital in Spain. Patients underwent open oral food challenge (OFC) tests for unpeeled peach and nuts/peanuts 1 year after the treatment started to assess food tolerance. A control group of patients diagnosed with LTP allergy who refused treatment with immunotherapy were included. Severity of symptoms and diet avoidance was recorded in both groups. <b><i>Results:</i></b> Twenty-nine patients with a median age of 24.7 years (range 5.5–43.1) were included: 100% were allergic to fruit; 72%, to peanut and/or nuts; 19 had a history of severe systemic reactions. Seven patients discontinued therapy; 3 (10%), due to adverse events. One year after SLIT start, 16 (73%) patients had negative OFC to peach; 95%, after 2 years; 69% had negative OFC to nuts/peanuts. The control group included 13 patients: 53.8% experienced reactions with new foods; severity of symptoms increased significantly (<i>p</i> &#x3c; 0.001), and diet restrictions were maintained in this group. <b><i>Conclusions:</i></b> SLIT with Pru p 3 shows a good safety profile, and avoid dietary restrictions in patients with LTP syndrome treated in the real-life setting.

The Role of Lipid Transfer Proteins as Food and Pollen Allergens Outside the Mediterranean Area

Purpose of Review To provide an overview of the prevalence and clinical manifestation of non-specific lipid transfer proteins (LTP)-mediated allergies outside the Mediterranean area and to address potential reasons for the different geographical significance of LTP-driven allergies. Recent Findings LTPs are major allergens in the Mediterranean area, which frequently can elicit severe reactions. Pru p 3 the LTP from peach is reported as genuine allergen and is considered a prototypic marker for LTP-mediated allergies. However, both food and pollen LTP allergies exist outside the Mediterranean area, but with lower clinical significance, different immunogenicity, and less clarified role. Summary Evidence has been reported that in areas with high exposure to pollen, in particular to mugwort, pollen-derived LTPs can act as a primary sensitizer to trigger secondary food allergies. Co-sensitization to unrelated allergens might be causative for less severe reactions in response to LTPs. However, the reason for the geographical different sensitization patterns to LTPs remains unclear.

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

<b><i>Background:</i></b> Component-resolved diagnosis reveals the IgE response to many inhaled, food, and other allergens, improving the understanding and diagnosis of allergic diseases. <b><i>Objective:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.

Impact of Different Lipid Ligands on the Stability and IgE-Binding Capacity of the Lentil Allergen Len c 3

Previously, we isolated the lentil allergen Len c 3, belonging to the class of lipid transfer proteins, cross-reacting with the major peach allergen Pru p 3 and binding lipid ligands. In this work, the allergenic capacity of Len c 3 and effects of different lipid ligands on the protein stability and IgE-binding capacity were investigated. Impacts of pH and heat treating on ligand binding with Len c 3 were also studied. It was shown that the recombinant Len c 3 (rLen c 3) IgE-binding capacity is sensitive to heating and simulating of gastroduodenal digestion. While being heated or digested, the protein showed a considerably lower capacity to bind specific IgE in sera of allergic patients. The presence of lipid ligands increased the thermostability and resistance of rLen c 3 to digestion, but the level of these effects was dependent upon the ligand’s nature. The anionic lysolipid LPPG showed the most pronounced protective effect which correlated well with experimental data on ligand binding. Thus, the Len c 3 stability and allergenic capacity can be retained in the conditions of food heat cooking and gastroduodenal digestion due to the presence of certain lipid ligands.