Anaphylaxis caused by lipid transfer proteins: an unpredictable clinical syndrome

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Inês Mota
Ângela Gaspar
Filipe Benito-Garcia
Magna Correia
Cristina Arêde
Susana Piedade
Grac¸a Sampaio
Grac¸a Pires
Cristina Santa-Marta
Luís-Miguel Borrego
Mário Morais-Almeida


Anaphylaxis, Food allergy, Food-dependent exercise-induced anaphylaxis, Lipid transfer proteins, Panallergens


Introduction: Lipid transfer proteins (LTPs) are panallergens found in many plant foods. They are a common cause of food-induced anaphylaxis (FIA) in adults living in the Mediterranean area. LTPs have also been proposed as a main cause of food-dependent exercise-induced anaphylaxis (FDEIA).

Objectives: Describe clinical characteristics and allergen sensitization profiles in patients with FIA related to LTP.

Materials and Methods: Forty-three patients were included, aged 3-52 years with a clinical history of FIA and proven sensitization to LTP. Patients were tested with a multiple plant food and pollen panel and specific IgE to LTP allergens. LTP sensitization was assessed by in vivo (Pru p 3, LTP extract) and/or by in vitro tests (specific IgE, ImmunoCAP/ISAC® ).

Results: Median age of first anaphylactic episode was 24 years (range 2-51), 44% had asthma, 74% were atopic and 42% had pollinosis (olive, mugwort, plane tree, wall pellitory and cypress). Co-sensitization to profilins was found in 22%. Overall in our center, LTP-induced anaphylaxis represents 17% of all causes of FIA. Foods implicated in anaphylactic reactions were: fresh fruits 51%, tree nuts 42%, vegetables (including peanut) 40% and seeds 14%. Seven patients had FDEIA.

Conclusions: LTPs are important allergens of FIA in Portugal. Clinical reactivity to several taxonomically unrelated plant foods may raise suspicion toward LTP sensitization. The association of LTP-induced anaphylaxis with pollinosis is relevant in our country. The unpredictable clinical expression depends on the effect of cofactors such as exercise. The management of avoidance plans can be challenging due to LTP being a widely cross-reacting allergen in plant foods.

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1. Asero R, Pravettoni V. Anaphylaxis to plant-foods and pollen allergens in patients with lipid transfer protein syndrome. Curr Opin Allergy Clin Immunol. 2013;13:379-85.

2. Van Winkle RC, Chang C. The biochemical basis and clinical evidence of food allergy due to lipid transfer proteins: a comprehensive review. Clin Rev Allergy Immunol. 2014;46:211-24.

3. Asero R, Antonicelli L, Arena A, Bommarito L, Caruso B, Crivellaro M, et al. EpidemAAITO-features of food allergy in Italian adults attending allergy clinics: a multi-centre study. Clin Exp Allergy. 2009;39:547-55.

4. Romano A, Scala E, Rumi G, Gaeta F, Caruso C, Alonzi C, et al. Lipid transfer proteins: the most frequent sensitizer in Italian subjects with food-dependent exercise-induced anaphylaxis. Clin Exp Allergy. 2012;42:1643-53.

5. Sánchez-López J, Asturias JA, Enrique E, Suárez-Cervera M, Bartra J. Cupressus arizonica pollen: a new pollen involved in the lipid transfer protein syndrome? J Investig Allergol Clin Immunol. 2011;21:522-6.

6. Fernandez-Rivas M. Fruit and vegetable allergy. Chem Immunol Allergy. 2015;101:162-70.

7. Fernández-Rivas M. Food allergy in Alergológica-2005. J Investig Allergol Clin Immunol. 2009;19 Suppl 2:37-44.

8. Pastorello EA, Farioli L, Pravettoni V, Scibilia J, Mascheri A, Borgonovo L, et al. Pru p 3-sensitised Italian peach-allergic patients are less likely to develop severe symptoms when also presenting IgE antibodies to Pru p 1 and Pru p 4. Int Arch Allergy Immunol. 2011;156:362-72.

9. Arena A. Anaphylaxis to apple: is fasting a risk factor for LTP-allergic patients? Eur Ann Allergy Clin Immunol. 2010;42: 155-8.

10. Egger M, Hauser M, Mari A, Ferreira F, Gadermaier G. The role of lipid transfer proteins in allergic diseases. Curr Allergy Asthma Rep. 2010;10:326-35.

11. Pascal M, Munoz-Cano R, Reina Z, Palacin A, Vilella R, Picado C, et al. Lipid transfer protein syndrome: clinical pattern, cofactor effect and profile of molecular sensitization to plant-foods and pollens. Clin Exp Allergy. 2012;42:1529-39.

12. Fernandez-Rivas M, Bolhaar S, Gonzalez-Mancebo E, Asero R, van Leeuwen A, Bohle B, et al. Apple allergy across Europe: how allergen sensitization profiles determine the clinical expression of allergies to plant foods. J Allergy Clin Immunol. 2006;118:481-8.

13. Asero R, Antonicelli L, Arena A, Bommarito L, Caruso B, Colombo G, et al. Causes of food-induced anaphylaxis in Italian adults: a multi-centre study. Int Arch Allergy Immunol. 2009;150: 271-7.

14. Feldweg AM. Food-dependent exercise-induced anaphylaxis: diagnosis and management in the outpatient setting. J Allergy Clin Immunol Pract. 2017;5:283-8.

15. Gomulka K, Wolanczyk-Medrala A, Barg W, Medrala W. Food-dependent, exercise-induced anaphylaxis triggered by coincidence of culprit food, physical effort and a very high dose of ibuprofen or menstruation: a case report. Postepy Dermatol Alergol. 2017;34:87-8.

16. Minty B. Food-dependent exercise-induced anaphylaxis. Can Fam Physician. 2017;63:42-3.

17. Harada S, Horikawa T, Ashida M, Kamo T, Nishioka E, Ichihashi M. Aspirin enhances the induction of type I allergic symptoms when combined with food and exercise in patients with food-dependent exercise-induced anaphylaxis. Br J Dermatol. 2001;145:336-9.

18. Munoz-Garcia E, Luengo-Sanchez O, Moreno-Perez N, CuestaHerranz J, Pastor-Vargas C, Cardona V. Lettuce allergy is a lipid transfer syndrome-related food allergy with high risk of severe reactions. J Investig Allergol Clin Immunol. 2016;27: 98-103.

19. Bianchi A, Di Rienzo Businco A, Bondanini F, Mistrello G, Carlucci A, Tripodi S. Rosaceae-associated exercise-induced anaphylaxis with positive SPT and negative IgE reactivity to Pru p 3. Eur Ann Allergy Clin Immunol. 2011;43:122-4.

20. Pascal M, Vazquez-Ortiz M, Folque MM, Jimenez-Feijoo R, Lozano J, Dominguez O, et al. sensitisation is common in plant food-allergic children from the Northeast of Spain. Allergol Immunopathol (Madr). 2016;44:351-8.

21. Vassilopoulou E, Zuidmeer L, Akkerdaas J, Tassios I, Rigby NR, Mills EN, et al. Severe immediate allergic reactions to grapes: part of a lipid transfer protein-associated clinical syndrome. Int Arch Allergy Immunol. 2007;143:92-102.

22. Garrido-Fernández S, García BE, Sanz ML, Echechipía S, Lizaso MT, Tabar AI. Are basophil activation and sulphidoleukotriene
determination useful tests for monitoring patients with peach allergy receiving sublingual immunotherapy with a Pru p 3- enriched peach extract? J Investig Allergol Clin Immunol. 2014;24:106-13.

23. Fernández-Rivas M, Garrido Fernández S, Nadal JA, Díaz de Durana MD, García BE, González-Mancebo E, et al. Randomized double-blind, placebo-controlled trial of sublingual immunotherapy with a Pru p 3 quantified peach extract. Allergy. 2009;64:876-83.

24. Pereira C, Bartolome B, Asturias JA, Ibarrola I, Tavares B, Loureiro G, et al. Specific sublingual immunotherapy with peach
LTP (Pru p 3) One-year treatment: a case report. Cases J. 2009;2:6553.

25. Costa AC, Melo A, Duarte F, Pereira-Barbosa M, Santos MCP. Efficacy and tolerance of sublingual immunotherapy with Pru p 3 in patients with peach severe allergy-clinical and immunological follow-up during 12 months. Rev Port Imunoalergologia. 2015;23:11-9.