Bile salts enhance the susceptibility of the peach allergenic lipid transfer protein, Pru p 3, to in vitro gastrointestinal proteolysis.

Sensitisation to the lipid transfer protein Pru p 3 is associated with severe allergic reactions to peach, the proteins stability being thought to play a role in its allergenicity. Lipid binding increases susceptibility of Pru p 3 to digestion and so the impact of bile salts on the in vitro gastrointestinal digestibility of Pru p 3 was investigated and digestion products mapped by SDS-PAGE and mass spectrometry. Bile salts enhanced the digestibility of Pru p 3 resulting in an ensemble of around 100 peptides spanning the protein's sequence which were linked by disulphide bonds into structures of ~ 5-6 kDa. IgE binding studies with a serum panel from peach allergic subjects showed digestion reduced, but did not abolish, the IgE reactivity of Pru p 3. These data show the importance of including bile salts in vitro digestion systems and emphasise the need to profile of digestion in a manner that allows identification of immunologically relevant disulphide-linked peptide aggregates.

Low Levels Matter: Clinical Relevance of Low Pru p 3 sIgE in Patients With Peach Allergy.

Many clinical lab settings still use 0.35 KUA/L as the cut-off for serum specific-IgE (sIgE) immunoassays, while the detection limit is 0.1 KUA/L. The clinical relevance of -low-level sIgE (0.1-0.35 KUA/L) remains controversial. Pru p 3 sIgE is considered to be the main routine tool for assessing lipid transfer protein (LTP) sensitization. We aimed to evaluate the clinical relevance of Pru p 3 sIgE low levels in a population diagnosed with LTP allergy. Adults diagnosed with LTP allergy and Pru p 3 sIgE ≥ 0.1 KUA/L between 2012 and 2019 were included. Clinical data were reviewed. nPru p 3 basophil activation test (BAT) was performed and basophil reactivity (BR) and sensitivity (BS) correlated with the peach allergy symptoms. Pru p 3 sIgE from 496 subjects was recorded, 114 (23.0%) between 0.1 and 0.34 KUA/L (grLOW), the rest ≥ 0.35 KUA/L (grB). A total of 44.7% in grLOW and 59.9% in grB were allergic. Urticaria was more frequent in grLOW. In grLOW, Pru p 3 sIgE was higher in patients with local compared with systemic symptoms. In grB, Pru p 3 sIgE was higher in allergic patients. Pru p 3/Total IgE ratios were higher in allergic vs. tolerant in both groups. In BAT, BR was similar in both groups. In grLOW, it was higher on allergic compared with tolerant (p = 0.0286), and on those having systemic vs. local symptoms (p = 0.0286). BS showed no significant difference between groups. Patients with low levels represent a non-negligible fraction and around 45% are peach allergic. BAT showed functional sIgE in them. Pru p 3 sensitizations should be carefully evaluated even when sIgE levels are low.

Detection of Wheat Lipid Transfer Protein (Tri a 14) Sensitization: Comparison between Currently Available Diagnostic Tools.

BACKGROUND: Wheat lipid transfer protein (LTP; Tri a 14) and ω5-gliadin have been described as major allergens in wheat allergy (WA) and relevant in wheat-induced anaphylaxis, frequently associated with cofactors. OBJECTIVE: The objective of this study was to compare tools currently available in routine diagnosis to detect Tri a 14 sensitization, its clinical relevance, and cosensitization to ω5-gliadin and other LTPs. METHODS: One hundred eighteen adults sensitized to rTri a 14 by ImmunoCAP® (cutoff ≥0.1 kUA/L) identified among 210 LTP allergic patients were included. We evaluated (1) wheat skin prick test (SPT), (2) specific IgE (sIgE) to wheat, rTri a 14, rTri a 19, peach, apple, walnut, hazelnut, and peanut LTPs using ImmunoCAP® and microarray ImmunoCAP®ISAC (cutoff ≥0.3I SU), and (3) wheat-related symptoms. RESULTS: Wheat SPT and sIgE were positive in 31% and 85% of subjects, respectively. rTri a 14 by microarray was detected in 25%. Eight percent showed cosensitization to ω5-gliadin. Thirty percent referred symptoms (gastrointestinal [13%], urticaria [11%], and anaphylaxis [8%]). Cofactors (45%) were significantly associated with systemic reactions. CONCLUSION: WA due to Tri a 14 is frequently related with systemic reactions and because are frequently related to cofactors, the culprit may not be suspected. Together with the poor performance to identify Tri a 14 sensitization of the current routine diagnostic tools based on the analysis of whole wheat extract, such as wheat SPT or sIgE, there is a high risk that WA may be overlooked. Thus, when WA is suspected, sIgE Tri a 14 assessment is recommended, together with wheat and ω5-gliadin, preferably in the singleplex format, and carefully evaluated considering ≥0.1 kUA/L as a cutoff.

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.

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.

Omalizumab and other biologics in drug desensitization.

PURPOSE OF REVIEW: Omalizumab has been proposed for controlling adverse reactions during drug desensitization. Our aim is to know the current evidence involving the use of omalizumab in drug-allergy desensitization. RECENT FINDINGS: Drug-allergy desensitization is not risk free, but it is a useful procedure and has been applied for drug hypersensitivity reactions with mast cells degranulation through IgE and non-IgE mechanisms. Since 2007, omalizumab has been considered as a potential strategy to prevent adverse reactions.Our review found few case reports and only one randomized double-blind, placebo-controlled study, using different omalizumab regimens prior to drug desensitization. This scarce evidence is insufficient to predict the effectiveness of omalizumab in rapid drug desensitization procedures, but it may be useful in future studies of omalizumab or related next-generation antibodies. SUMMARY: Omalizumab or other IgE-targeting biologics, either a fixed dose of 300 mg omalizumab or a dose-related total IgE level and body mass weight may be an option for patients with IgE-mediated or mast cell drug reactions in troublesome desensitization.

Immune-Mediated Mechanisms in Cofactor-Dependent Food Allergy and Anaphylaxis: Effect of Cofactors in Basophils and Mast Cells.

Cofactors may explain why in some cases food ingestion leads to anaphylaxis while in others elicits a milder reaction or tolerance. With cofactors, reactions become more severe and/or have a lower allergen threshold. Cofactors are present in up to 58% of food anaphylaxis (FAn). Exercise, NSAIDs, and alcohol are the most frequently described, although the underlying mechanisms are poorly known. Several hypotheses have suggested the influence of these cofactors on basophils and mast cells (MCs). Exercise has been suggested to enhance MC activation by increasing plasma osmolarity, redistributing blood flow, and activating adenosine and eicosanoid metabolism. NSAIDs' cofactor effect has been related with cyclooxygenase inhibition and therefore, prostaglandin E2 (PGE2) production. Indeed, overexpression of adenosine receptor 3 (A3) gene has been described in NSAID-dependent FAn; A3 activation potentiates FcϵRI-induced MC degranulation. Finally, alcohol has been related with an increase of histamine levels by inhibition of diamino oxidase (DAO) and also with and increase of extracellular adenosine by inhibition of its uptake. However, most of these mechanisms have limited evidence, and further studies are urgently needed. In conclusion, the study of the immune-related mechanisms involved in food allergic reactions enhanced by cofactors is of the utmost interest. This knowledge will help to design both tailored treatments and prophylactic strategies that, nowadays, are non-existent.

Allergological Study of 565 Elderly Patients Previously Labeled as Allergic to Penicillins.

PURPOSE: Elderly people thought to have an allergy to beta-lactams (BLs) may tolerate the drugs in subsequent exposures due to initial false labeling of allergies, the spontaneous loss of sensitivity to BLs over time or age-related decline in sensitization. As a result, they may be treated with less appropriate antibiotics, causing more side effects and entailing increased costs for health systems. The aim of this investigation was to assess whether patients in the third and fourth age with previously confirmed allergies to BLs had lost sensitization and could tolerate these antibiotics. PATIENTS AND METHODS: Patients allergic to BLs were divided into group A (aged 60-79 years) and B (aged ≥80 years). Clinical history, skin testing, drug challenge tests (DCT) and evaluation of resensitization were used to classify participants as showing immediate reactions, non-immediate reactions, or tolerance. We compared clinical entities, drugs involved, and final outcome by age group. RESULTS: Of 1362 cases evaluated, 565 underwent an allergological study. The skin was the most common organ involved. Anaphylaxis and side chain reactions were more frequent in group A (p<0.01), as were positive DCT. Classical benzylpenicillin determinants (benzylpenicilloyl and/or minor determinant mixture) were more frequent triggers in group B (p< 0.01). Resensitization after challenge occurred in very few participants. CONCLUSION: The risk for allergy to BLs decreases with age and a history of anaphylaxis by BLs is a predictor of positive results in skin tests (ST). Both immunoglobin E (IgE) and T-cell-mediated responses can disappear in elderly people, who can develop tolerance to these antibiotics. These results are of clinical relevance to patients who need to be treated with antibiotics from this family.