Skip to main content

Advertisement

Log in

The Biochemical Basis and Clinical Evidence of Food Allergy Due to Lipid Transfer Proteins: A Comprehensive Review

  • Published:
Clinical Reviews in Allergy & Immunology Aims and scope Submit manuscript

Abstract

Plant lipid transfer proteins (LTPs) are ubiquitous proteins that are found in divergent plant species. Although the exact function of LTPs is not fully understood, LTPs are conserved across a broad range of plant species. Because LTPs share structural features, there is an increased probability for significant allergic cross-reactivity. The molecular features of LTPs also decrease the probability of degradation due to cooking or digestion, thereby increasing the probability of systemic absorption and severe allergic reactions. LTP allergy, unlike other forms of anaphylaxis, tends to occur more frequently in areas of lower latitude. The geographic distribution of LTP allergy, along with evidence of increased sensitization after respiratory exposure, has led to the hypothesis that LTP-related food allergy may be secondary to sensitization via the respiratory route. Clinical reactions associated with LTPs have broad clinical phenotypes and can be severe in nature. Life-threatening clinical reactions have been associated with ingestion of a multitude of plant products. Component-resolved diagnosis has played a significant role in research applications for LTP allergy. In the future, component-resolved diagnosis may play a significant role in day-to-day clinical care. Also, quantitative analysis of LTPs in foodstuffs may allow for the identification and/or production of low-LTP foods, thereby decreasing the risk to patients with LTP allergy. Furthermore, sublingual immunotherapy may provide a therapeutic option for patients with LTP allergy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Figure 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Zuidmeer L, van Ree R (2007) Lipid transfer protein allergy: primary food allergy or pollen/food syndrome in some cases. Curr Opin Allergy Clin Immunol 7(3):269–273

    Article  PubMed  CAS  Google Scholar 

  2. Garcia-Olmedo F et al (1995) The defensive role of nonspecific lipid-transfer proteins in plants. Trends Microbiol 3(2):72–74

    Article  PubMed  CAS  Google Scholar 

  3. Egger M et al (2010) The role of lipid transfer proteins in allergic diseases. Curr Allergy Asthma Rep 10(5):326–335

    Article  PubMed  CAS  Google Scholar 

  4. Bernardi ML et al (2011) Allergenic lipid transfer proteins from plant-derived foods do not immunologically and clinically behave homogeneously: the kiwifruit LTP as a model. PLoS One 6(11):e27856

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  5. Borges JP et al (2006) The lipid transfer proteins (LTP) essentially concentrate in the skin of Rosaceae fruits as cell surface exposed allergens. Plant Physiol Biochem 44(10):535–542

    Article  PubMed  CAS  Google Scholar 

  6. Cavatorta V et al (2009) Unambiguous characterization and tissue localization of Pru P 3 peach allergen by electrospray mass spectrometry and MALDI imaging. J Mass Spectrom 44(6):891–897

    Article  PubMed  CAS  Google Scholar 

  7. Pasquato N et al (2006) Crystal structure of peach Pru p 3, the prototypic member of the family of plant non-specific lipid transfer protein pan-allergens. J Mol Biol 356(3):684–694

    Article  PubMed  CAS  Google Scholar 

  8. Pravettoni V et al (2009) Tomato allergy: detection of IgE-binding lipid transfer proteins in tomato derivatives and in fresh tomato peel, pulp, and seeds. J Agric Food Chem 57(22):10749–10754

    Article  PubMed  CAS  Google Scholar 

  9. Sancho AI et al (2005) The effect of thermal processing on the IgE reactivity of the non-specific lipid transfer protein from apple, Mal d 3. Allergy 60(10):1262–1268

    Article  PubMed  CAS  Google Scholar 

  10. Asero R et al (2000) Lipid transfer protein: a pan-allergen in plant-derived foods that is highly resistant to pepsin digestion. Int Arch Allergy Immunol 122(1):20–32

    Article  PubMed  CAS  Google Scholar 

  11. Wijesinha-Bettoni R et al (2010) The structural characteristics of nonspecific lipid transfer proteins explain their resistance to gastroduodenal proteolysis. Biochemistry 49(10):2130–2139

    Article  PubMed  CAS  Google Scholar 

  12. Gincel E et al (1994) Three-dimensional structure in solution of a wheat lipid-transfer protein from multidimensional 1H-NMR data. A new folding for lipid carriers. Eur J Biochem 226(2):413–422

    Article  PubMed  CAS  Google Scholar 

  13. Shin DH et al (1995) High-resolution crystal structure of the non-specific lipid-transfer protein from maize seedlings. Structure 3(2):189–199

    Article  PubMed  CAS  Google Scholar 

  14. Gomar J et al (1996) Solution structure and lipid binding of a nonspecific lipid transfer protein extracted from maize seeds. Protein Sci 5(4):565–577

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  15. Poznanski J et al (1999) Solution structure of a lipid transfer protein extracted from rice seeds. Comparison with homologous proteins. Eur J Biochem 259(3):692–708

    Article  PubMed  CAS  Google Scholar 

  16. Borges JP et al (2008) Lipid transfer proteins from Rosaceae fruits share consensus epitopes responsible for their IgE-binding cross-reactivity. Biochem Biophys Res Commun 365(4):685–690

    Article  PubMed  CAS  Google Scholar 

  17. Tordesillas L et al (2009) Molecular basis of allergen cross-reactivity: non-specific lipid transfer proteins from wheat flour and peach fruit as models. Mol Immunol 47(2–3):534–540

    Article  PubMed  CAS  Google Scholar 

  18. Borghesan F et al (2008) Respiratory allergy to lipid transfer protein. Int Arch Allergy Immunol 147(2):161–165

    Article  PubMed  Google Scholar 

  19. Scala E et al (2010) Cross-sectional survey on immunoglobulin E reactivity in 23,077 subjects using an allergenic molecule-based microarray detection system. Clin Exp Allergy 40(6):911–921

    Article  PubMed  CAS  Google Scholar 

  20. Camargo CA Jr et al (2007) Regional differences in EpiPen prescriptions in the United States: the potential role of vitamin D. J Allergy Clin Immunol 120(1):131–136

    Article  PubMed  Google Scholar 

  21. Asero R et al (2009) EpidemAAITO: features of food allergy in Italian adults attending allergy clinics: a multi-centre study. Clin Exp Allergy 39(4):547–555

    Article  PubMed  CAS  Google Scholar 

  22. Monzon Ballarin S et al (2011) Anaphylaxis associated with the ingestion of Goji berries (Lycium barbarum). J Investig Allergol Clin Immunol 21(7):567–570

    PubMed  CAS  Google Scholar 

  23. Gebhardt C et al (2009) 10 kDa lipid transfer protein: the main allergenic structure in a German patient with anaphylaxis to blueberry. Allergy 64(3):498–499

    Article  PubMed  CAS  Google Scholar 

  24. Arena A (2010) Anaphylaxis to apple: is fasting a risk factor for LTP-allergic patients? Eur Ann Allergy Clin Immunol 42(4):155–158

    PubMed  CAS  Google Scholar 

  25. Asero R, Mistrello G, Amato S (2011) Anaphylaxis caused by tomato lipid transfer protein. Eur Ann Allergy Clin Immunol 43(4):125–126

    PubMed  CAS  Google Scholar 

  26. Yagami A (2010) Anaphylaxis to lipid transfer protein from sunflower seeds. Allergy 65(10):1340–1341

    Article  PubMed  CAS  Google Scholar 

  27. Palacin A et al (2010) Anaphylaxis to wheat flour-derived foodstuffs and the lipid transfer protein syndrome: a potential role of wheat lipid transfer protein Tri a 14. Int Arch Allergy Immunol 152(2):178–183

    Article  PubMed  CAS  Google Scholar 

  28. Hansen KS et al (2009) Component-resolved in vitro diagnosis of hazelnut allergy in Europe. J Allergy Clin Immunol 123(5):1134–1141, 1141 e1-3

    Article  PubMed  CAS  Google Scholar 

  29. Asero R et al (2001) A case of allergy to beer showing cross-reactivity between lipid transfer proteins. Ann Allergy Asthma Immunol 87(1):65–67

    Article  PubMed  CAS  Google Scholar 

  30. Schad SG et al (2005) Wine anaphylaxis in a German patient: IgE-mediated allergy against a lipid transfer protein of grapes. Int Arch Allergy Immunol 136(2):159–164

    Article  PubMed  Google Scholar 

  31. Enrique E et al (2005) Lipid transfer protein is involved in rhinoconjunctivitis and asthma produced by rice inhalation. J Allergy Clin Immunol 116(4):926–928

    Article  PubMed  CAS  Google Scholar 

  32. Asero R (2011) Hypersensitivity to lipid transfer protein is frequently associated with chronic urticaria. Eur Ann Allergy Clin Immunol 43(1):19–21

    PubMed  CAS  Google Scholar 

  33. Gadermaier G et al (2011) Sensitization prevalence, antibody cross-reactivity and immunogenic peptide profile of Api g 2, the non-specific lipid transfer protein 1 of celery. PLoS One 6(8):e24150

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  34. Sanchez-Monge R et al (1999) Lipid-transfer proteins are relevant allergens in fruit allergy. J Allergy Clin Immunol 103(3 Pt 1):514–519

    Article  PubMed  CAS  Google Scholar 

  35. Pastorello EA et al (1999) The major allergen of peach (Prunus persica) is a lipid transfer protein. J Allergy Clin Immunol 103(3 Pt 1):520–526

    Article  PubMed  CAS  Google Scholar 

  36. Diaz-Perales A et al (2002) cDNA cloning and heterologous expression of the major allergens from peach and apple belonging to the lipid-transfer protein family. Clin Exp Allergy 32(1):87–92

    Article  PubMed  CAS  Google Scholar 

  37. Asero R et al (2002) Immunological cross-reactivity between lipid transfer proteins from botanically unrelated plant-derived foods: a clinical study. Allergy 57(10):900–906

    Article  PubMed  CAS  Google Scholar 

  38. Asero R et al (2006) Peach fuzz contains large amounts of lipid transfer protein: is this the cause of the high prevalence of sensitization to LTP in Mediterranean countries? Eur Ann Allergy Clin Immunol 38(4):118–121

    PubMed  CAS  Google Scholar 

  39. Fernandez-Rivas M et al (2009) Randomized double-blind, placebo-controlled trial of sublingual immunotherapy with a Pru p 3 quantified peach extract. Allergy 64(6):876–883

    Article  PubMed  CAS  Google Scholar 

  40. Andersen MB, Hall S, Dragsted LO (2011) Identification of European allergy patterns to the allergen families PR-10, LTP, and profilin from Rosaceae fruits. Clin Rev Allergy Immunol 41(1):4–19

    Article  PubMed  CAS  Google Scholar 

  41. Zuidmeer-Jongejan L et al (2012) FAST: towards safe and effective subcutaneous immunotherapy of persistent life-threatening food allergies. Clin Transl Allergy 2(1):5

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  42. Pastorello EA et al (2000) Evidence for a lipid transfer protein as the major allergen of apricot. J Allergy Clin Immunol 105(2 Pt 1):371–377

    Article  PubMed  CAS  Google Scholar 

  43. Scheurer S et al (2001) Recombinant allergens Pru av 1 and Pru av 4 and a newly identified lipid transfer protein in the in vitro diagnosis of cherry allergy. J Allergy Clin Immunol 107(4):724–731

    Article  PubMed  CAS  Google Scholar 

  44. Pastorello EA et al (2001) Characterization of the major allergen of plum as a lipid transfer protein. J Chromatogr B Biomed Sci Appl 756(1–2):95–103

    Article  PubMed  CAS  Google Scholar 

  45. Marzban G et al (2008) Identification of four IgE-reactive proteins in raspberry (Rubus ideaeus L.). Mol Nutr Food Res 52(12):1497–1506

    Article  PubMed  CAS  Google Scholar 

  46. Ciardiello MA et al (2010) Biochemical, immunological and clinical characterization of a cross-reactive nonspecific lipid transfer protein 1 from mulberry. Allergy 65(5):597–605

    Article  PubMed  CAS  Google Scholar 

  47. Ramazzina I et al (2012) Isoform identification, recombinant production and characterization of the allergen lipid transfer protein 1 from pear (Pyr c 3). Gene 491(2):173–181

    Article  PubMed  CAS  Google Scholar 

  48. Zuidmeer L et al (2006) The role of profilin and lipid transfer protein in strawberry allergy in the Mediterranean area. Clin Exp Allergy 36(5):666–675

    Article  PubMed  CAS  Google Scholar 

  49. Ahrazem O et al (2005) Lipid transfer proteins and allergy to oranges. Int Arch Allergy Immunol 137(3):201–210

    Article  PubMed  CAS  Google Scholar 

  50. Ebo DG et al (2007) Anaphylaxis from mandarin (Citrus reticulata): identification of potential responsible allergens. Int Arch Allergy Immunol 144(1):39–43

    Article  PubMed  CAS  Google Scholar 

  51. Kleinheinz A et al (2009) Anaphylactic reaction to (mixed) fruit juice containing dragon fruit. J Allergy Clin Immunol 124(4):841–842

    Article  PubMed  Google Scholar 

  52. Enrique E et al (2006) Allergy to lipid transfer proteins: cross-reactivity among pomegranate, hazelnut, and peanut. Ann Allergy Asthma Immunol 96(1):122–123

    Article  PubMed  Google Scholar 

  53. Zoccatelli G et al (2007) Isolation and identification of two lipid transfer proteins in pomegranate (Punica granatum). J Agric Food Chem 55(26):11057–11062

    Article  PubMed  CAS  Google Scholar 

  54. Lorenz Y et al (2006) Skin prick tests reveal stable and heritable reduction of allergenic potency of gene-silenced tomato fruits. J Allergy Clin Immunol 118(3):711–718

    Article  PubMed  CAS  Google Scholar 

  55. Pastorello EA et al (2003) Identification of grape and wine allergens as an endochitinase 4, a lipid-transfer protein, and a thaumatin. J Allergy Clin Immunol 111(2):350–359

    Article  PubMed  CAS  Google Scholar 

  56. Vassilopoulou E et al (2006) Effect of in vitro gastric and duodenal digestion on the allergenicity of grape lipid transfer protein. J Allergy Clin Immunol 118(2):473–480

    Article  PubMed  CAS  Google Scholar 

  57. Wigand P et al (2009) Analysis of protein composition of red wine in comparison with rose and white wines by electrophoresis and high-pressure liquid chromatography–mass spectrometry (HPLC-MS). J Agric Food Chem 57(10):4328–4333

    Article  PubMed  CAS  Google Scholar 

  58. Palacin A et al (2011) Sensitization profiles to purified plant food allergens among pediatric patients with allergy to banana. Pediatr Allergy Immunol 22(2):186–195

    Article  PubMed  Google Scholar 

  59. Ballmer-Weber BK et al (2005) Component-resolved in vitro diagnosis in carrot allergy: does the use of recombinant carrot allergens improve the reliability of the diagnostic procedure? Clin Exp Allergy 35(7):970–978

    Article  PubMed  CAS  Google Scholar 

  60. Asero R et al (2007) Detection of some safe plant-derived foods for LTP-allergic patients. Int Arch Allergy Immunol 144(1):57–63

    Article  PubMed  Google Scholar 

  61. Cordobes-Duran C et al (2007) Detection of a 12-kilodalton lipid transfer protein allergen in parsley. J Investig Allergol Clin Immunol 17(4):282–283

    PubMed  CAS  Google Scholar 

  62. Enrique E et al (2007) Involvement of lipid transfer protein in onion allergy. Ann Allergy Asthma Immunol 98(2):202

    Article  PubMed  Google Scholar 

  63. Diaz-Perales A et al (2002) Characterization of asparagus allergens: a relevant role of lipid transfer proteins. J Allergy Clin Immunol 110(5):790–796

    Article  PubMed  CAS  Google Scholar 

  64. Hartz C et al (2007) Molecular characterisation of Lac s 1, the major allergen from lettuce (Lactuca sativa). Mol Immunol 44(11):2820–2830

    Article  PubMed  CAS  Google Scholar 

  65. Palacin A et al (2006) Cabbage lipid transfer protein Bra o 3 is a major allergen responsible for cross-reactivity between plant foods and pollens. J Allergy Clin Immunol 117(6):1423–1429

    Article  PubMed  CAS  Google Scholar 

  66. Garcia-Casado G et al (2001) Isolation and characterization of barley lipid transfer protein and protein Z as beer allergens. J Allergy Clin Immunol 108(4):647–649

    Article  PubMed  CAS  Google Scholar 

  67. Palacin A et al (2007) Wheat lipid transfer protein is a major allergen associated with baker’s asthma. J Allergy Clin Immunol 120(5):1132–1138

    Article  PubMed  CAS  Google Scholar 

  68. Pastorello EA et al (2001) A lipid transfer protein involved in occupational sensitization to spelt. J Allergy Clin Immunol 108(1):145–146

    Article  PubMed  CAS  Google Scholar 

  69. Pastorello EA et al (2000) The maize major allergen, which is responsible for food-induced allergic reactions, is a lipid transfer protein. J Allergy Clin Immunol 106(4):744–751

    Article  PubMed  CAS  Google Scholar 

  70. Pastorello EA et al (2003) Lipid-transfer protein is the major maize allergen maintaining IgE-binding activity after cooking at 100 degrees C, as demonstrated in anaphylactic patients and patients with positive double-blind, placebo-controlled food challenge results. J Allergy Clin Immunol 112(4):775–783

    Article  PubMed  CAS  Google Scholar 

  71. Kuppannan K et al (2011) Quantification and characterization of maize lipid transfer protein, a food allergen, by liquid chromatography with ultraviolet and mass spectrometric detection. Anal Chem 83(2):516–524

    Article  PubMed  CAS  Google Scholar 

  72. Sanchez-Monge R et al (2006) Differential allergen sensitization patterns in chestnut allergy with or without associated latex-fruit syndrome. J Allergy Clin Immunol 118(3):705–710

    Article  PubMed  CAS  Google Scholar 

  73. Schocker F et al (2004) Recombinant lipid transfer protein Cor a 8 from hazelnut: a new tool for in vitro diagnosis of potentially severe hazelnut allergy. J Allergy Clin Immunol 113(1):141–147

    Article  PubMed  CAS  Google Scholar 

  74. Schulten V et al (2011) Pru p 3, the nonspecific lipid transfer protein from peach, dominates the immune response to its homolog in hazelnut. Allergy 66(8):1005–1013

    Article  PubMed  CAS  Google Scholar 

  75. Pastorello EA et al (2004) Lipid transfer protein and vicilin are important walnut allergens in patients not allergic to pollen. J Allergy Clin Immunol 114(4):908–914

    Article  PubMed  CAS  Google Scholar 

  76. Garrido-Fernandez S et al (2009) The role of lipid transfer proteins in the almond tree and almond fruit as contact and airborne allergens. J Investig Allergol Clin Immunol 19(1):61–63

    PubMed  CAS  Google Scholar 

  77. Verma AK et al. (2012) A comprehensive review of legume allergy. Clin Rev Allergy Immunol doi:10.1007/s12016-012-8310-6

  78. Krause S et al (2009) Lipid transfer protein (Ara h 9) as a new peanut allergen relevant for a Mediterranean allergic population. J Allergy Clin Immunol 124(4):771–778, e5

    Article  PubMed  CAS  Google Scholar 

  79. Vereda A et al (2011) Peanut allergy: clinical and immunologic differences among patients from 3 different geographic regions. J Allergy Clin Immunol 127(3):603–607

    Article  PubMed  CAS  Google Scholar 

  80. Akkerdaas J et al (2012) Lentil (Lens culinaris) lipid transfer protein Len c 3: a novel legume allergen. Int Arch Allergy Immunol 157(1):51–57

    Article  PubMed  CAS  Google Scholar 

  81. Pastorello EA et al (2010) Green bean (Phaseolus vulgaris): a new source of IgE-binding lipid transfer protein. J Agric Food Chem 58(7):4513–4516

    Article  PubMed  CAS  Google Scholar 

  82. Sirvent S et al (2009) nsLTP and profilin are allergens in mustard seeds: cloning, sequencing and recombinant production of Sin a 3 and Sin a 4. Clin Exp Allergy 39(12):1929–1936

    Article  PubMed  CAS  Google Scholar 

  83. Vereda A et al (2011) Improvement of mustard (Sinapis alba) allergy diagnosis and management by linking clinical features and component-resolved approaches. J Allergy Clin Immunol 127(5):1304–1307

    Article  PubMed  Google Scholar 

  84. Vissers YM et al (2011) IgE component-resolved allergen profile and clinical symptoms in soy and peanut allergic patients. Allergy 66(8):1125–1127

    Article  PubMed  CAS  Google Scholar 

  85. Ballmer-Weber BK et al (2002) Component-resolved diagnosis with recombinant allergens in patients with cherry allergy. J Allergy Clin Immunol 110(1):167–173

    Article  PubMed  CAS  Google Scholar 

  86. Asero R, Jimeno L, Barber D (2008) Component-resolved diagnosis of plant food allergy by SPT. Eur Ann Allergy Clin Immunol 40(4):115–121

    PubMed  CAS  Google Scholar 

  87. Palacin A et al (2009) Recombinant lipid transfer protein Tri a 14: a novel heat and proteolytic resistant tool for the diagnosis of baker’s asthma. Clin Exp Allergy 39(8):1267–1276

    Article  PubMed  CAS  Google Scholar 

  88. Cox L (2011) Overview of serological-specific IgE antibody testing in children. Curr Allergy Asthma Rep 11(6):447–453

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christopher Chang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Van Winkle, R.C., Chang, C. The Biochemical Basis and Clinical Evidence of Food Allergy Due to Lipid Transfer Proteins: A Comprehensive Review. Clinic Rev Allerg Immunol 46, 211–224 (2014). https://doi.org/10.1007/s12016-012-8338-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12016-012-8338-7

Keywords

Navigation