Lipid transfer protein allergy

Lipid transfer proteins (LTPs) are a large protein family found in multiple plants (representing a panallergen) with an important role in the plant's defense against stressors. The LTPs are small proteins of 6 to 9 kilodaltons that are resistant to heat and digestion. They are present in fruits, vegetables, nuts, seeds, legumes, cereals, and various pollens.1Skypala IJ Bartra J Ebo DG Faber MA Fernández-Rivas M Gomez F et al.The diagnosis and management of allergic reactions in patients sensitized to non-specific lipid transfer proteins.Allergy. 2021; 76: 2433-2446Crossref PubMed Scopus (26) Google Scholar The highest amount of allergen is contained in the fruit's skin (“peach fuzz”), peel, and pip. Multiple studies have originated from Italy and Spain describing peach LTP (Pru p 3) as the most common sensitizing agent.2Asero R Pravettoni V Scala E Villalta D Lipid transfer protein allergy: a review of current controversies.Clin Exp Allergy. 2022; 52: 222-230Crossref PubMed Scopus (6) Google Scholar,3Fernández-Rivas M González-Mancebo E Rodríguez-Pérez R Benito C Sánchez-Monge R Salcedo G et al.Clinically relevant peach allergy is related to peach lipid transfer protein, Pru p 3, in the Spanish population.J Allergy Clin Immunol. 2003; 112: 789-795Abstract Full Text Full Text PDF PubMed Scopus (216) Google Scholar Sensitization usually occurs by means of the gastrointestinal route but may also occur by means of the cutaneous route (peach-induced contact urticaria is very common in Italy and Spain) and the respiratory/inhalant route (especially in regions rich in peach orchards).1Skypala IJ Bartra J Ebo DG Faber MA Fernández-Rivas M Gomez F et al.The diagnosis and management of allergic reactions in patients sensitized to non-specific lipid transfer proteins.Allergy. 2021; 76: 2433-2446Crossref PubMed Scopus (26) Google Scholar Some sensitized individuals may remain asymptomatic and not develop LTP allergy or syndrome (defined as clinical allergy to at least 2 unrelated LTP food allergens), a phenomenon often noted in the Northern areas of Europe.2Asero R Pravettoni V Scala E Villalta D Lipid transfer protein allergy: a review of current controversies.Clin Exp Allergy. 2022; 52: 222-230Crossref PubMed Scopus (6) Google Scholar Testing asymptomatic individuals are not recommended since it may result in unnecessary food exclusions. A detailed history is a key in the diagnosis of LTP allergy. The LTPs are the most common cause of primary food allergy and food-induced anaphylaxis in Southern European countries (Mediterranean and Atlantic areas). The clinical presentation of LTP allergy varies significantly among patients—from urticaria/angioedema to oral allergy symptoms, to severe reactions and anaphylaxis.1Skypala IJ Bartra J Ebo DG Faber MA Fernández-Rivas M Gomez F et al.The diagnosis and management of allergic reactions in patients sensitized to non-specific lipid transfer proteins.Allergy. 2021; 76: 2433-2446Crossref PubMed Scopus (26) Google Scholar,4Asero R Piantanida M Pinter E Pravettoni V The clinical relevance of lipid transfer protein.Clin Exp Allergy. 2018; 48: 6-12Crossref PubMed Scopus (71) Google Scholar Symptoms may occur soon after ingestion of raw, cooked, and processed foods. Young children generally present with milder symptoms than adolescents and adults. Frequently, a cofactor, such as exercise, alcohol, stress, or nonsteroidal anti-inflammatory drugs are required to induce symptoms—this can create difficulties with the diagnosis since symptoms may be absent without the cofactor.1Skypala IJ Bartra J Ebo DG Faber MA Fernández-Rivas M Gomez F et al.The diagnosis and management of allergic reactions in patients sensitized to non-specific lipid transfer proteins.Allergy. 2021; 76: 2433-2446Crossref PubMed Scopus (26) Google Scholar Interestingly, sensitization to other panallergens such as Bet v1 and profilins has been found to be protective against severe reactions in some studies, but not others.5Scala E Abeni D Guerra EC Locanto M Pirrotta L Meneguzzi G et al.Cosensitization to profilin is associated with less severe reactions to foods in nsLTPs and storage proteins reactors and with less severe respiratory allergy.Allergy. 2018; 73: 1921-1923Crossref PubMed Scopus (16) Google Scholar,6Skypala IJ Cecchi L Shamji MH Scala E Till S Lipid Transfer Protein allergy in the United Kingdom: characterization and comparison with a matched Italian cohort.Allergy. 2019; 74: 1340-1351Crossref PubMed Scopus (44) Google Scholar For a long time, the syndrome was only known in Southern Europe, where it is highly prevalent, but more recently, cases have been described in other areas of the world, including Northern Europe, the People's Republic of China, Japan, South Africa, and Australia. In the United States, a recent study evaluating serum samples from 10,503 hazelnut-positive individuals reported that 10% were sensitized to Cor a 8, although clinical allergy was not confirmed.7Valcour A Lidholm J Borres MP Hamilton RG Sensitization profiles to hazelnut allergens across the United States.Ann Allergy Asthma Immunol. 2019; 122: 111-116.e1Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar A separate study describing molecular component profiles of patients with peanut allergy from 3 different countries (United States, Spain, and Sweden) reported a 7.7% rate of sensitization to Ara h 9 in the 30 patients included from the United States, compared with 60% in Spain and 14.3% in Sweden.8Vereda A van Hage M Ahlstedt S Ibañez MD Cuesta-Herranz J van Odijk J et al.Peanut allergy: clinical and immunologic differences among patients from 3 different geographic regions.J Allergy Clin Immunol. 2011; 127: 603-607Abstract Full Text Full Text PDF PubMed Scopus (238) Google Scholar It is likely that LTP allergy remains underrecognized in the United States. In their retrospective chart review study, Muñoz-Osores et al9Muñoz-Osores E Aguirre J Concha S Borzutzky A Hoyos-Bachiloglu R Lipid transfer protein allergy and anaphylaxis in children.Ann Allergy Asthma Immunol. 2023; 130: 520-522Abstract Full Text Full Text PDF Scopus (1) Google Scholar described a cohort of 32 children with LTP allergy from Latin America (Chile), with a median age of 7 years. Their cohort is different from European-described populations in many ways: (1) a much larger proportion presenting with anaphylaxis (53%); (2) non-Rosaceae family fruits, legumes, and tree nuts are the most common allergens; (3) a high incidence of anaphylaxis is reported in patients sensitized to profilins (contrary to European reports); and (4) the most common triggers for anaphylaxis seem to be tree nuts (walnut and almond) rather than peach. Some of these differences may be attributed to different dietary patterns and eating habits in Chile. The study has certain limitations including the following: (1) the design is a retrospective chart review, (2) the data are collected from a single center in an urban area (Santiago), (3) the diagnosis is on the basis of the reported history of allergic symptoms and LTP sensitization (oral food challenges were not performed), (4) there is potential for selection bias because all patients were recruited from a specialist allergy clinic, and (5) the cohort only included a small number of subjects.9Muñoz-Osores E Aguirre J Concha S Borzutzky A Hoyos-Bachiloglu R Lipid transfer protein allergy and anaphylaxis in children.Ann Allergy Asthma Immunol. 2023; 130: 520-522Abstract Full Text Full Text PDF Scopus (1) Google Scholar However, to our knowledge, it represents the first report of pediatric patients with LTP allergy from Latin America, providing some interesting insights into the clinical presentation, causes, cofactors, and rate of anaphylaxis in an area of the world where LTP is not endemic. An interesting finding that was not discussed in this study is that LTP sensitization may occur by the inhalation or contact with cannabis LTP (Can s 3) even with passive smoke/exposure (for example, in young children), potentially leading to the development of LTP food allergy.10Cabrera-Freitag P Infante S Barolomé B Álvarez-Perea A Fuentes-Aparicio V Zapatero Remón L Anaphylaxis related to passive second-hand exposure to Cannabis sativa cigarette smoke in adolescents.J Investig Allergol Clin Immunol. 2019; 29: 298-300Crossref PubMed Scopus (6) Google Scholar This is a relevant point for areas in the world in which LTP allergy is not frequent. It is already known that significant geographic differences exist among patients with LTP not only in different countries but also different areas within the same country. For example, in Italy, the prevalence of LTP allergy is significantly higher in the southern part of the country compared with the Northern areas. These differences are important since they offer an opportunity to better evaluate and understand this complex condition, with its varying ways of clinical presentation, pathophysiology, triggering allergens, cofactors, and protective factors. The importance of LTP allergy lies in its potential to cause severe allergic reactions, the challenges it presents for correct diagnosis and the fact that it is becoming an emerging food allergy outside the Mediterranean area. Further studies are required in larger cohorts from various parts of the world to enhance our knowledge of this allergic condition in diverse populations and distinct environmental settings. Lipid transfer protein allergy and anaphylaxis in childrenAnnals of Allergy, Asthma & ImmunologyVol. 130Issue 4PreviewLipid transfer protein (LTP) is a pan-allergen widely distributed in plants, including Rosaceae family fruits, non-Rosaceae family fruits (such as Vitaceae, Solanaceae, and Oleaceae), tree nuts, legumes, vegetables, cereals, seeds, and latex.1 Food allergy (FA) to LTP is an immunoglobulin E (igE)-mediated allergy with increasing incidence in children.2 Studies from Spain report that LTP allergy explains 5% of cases of pediatric FA and that up to 26% of children with a history of reactions to vegetables or fruits are LTP sensitized,2 which can develop through direct gastrointestinal, cutaneous, or respiratory exposure to LTP,2 with current evidence arguing against a primary pollen sensitization. Full-Text PDF