Background: Lipid transfer proteins (LTPs) are small molecules of approximately 10 kD that demonstrate high stability. They have recently been identified as allergens in the Rosaceae subfamilies of the Prunoideae (peach, apricot, plum) and of the Pomoideae (apple). They belong to a family of structurally highly conserved proteins that are also present in non-Rosaceae vegetable foods. Objective: The aim of this study was to investigate the cross-reactivity to non-Rosaceae LTPs, and to study the role of protein stability in allergenicity. Methods: Thirty-eight patients with a positive SPT to Rosaceae fruit extracts enriched for LTP were characterized by interview and SPT. To investigate IgE cross-reactivity between Rosaceae and non-Rosaceae LTPs, RAST and RAST inhibition as well as ELISA and ELISA inhibition were performed, using whole food extracts and purified LTPs. Both purified natural LTPs (peach, carrot and broccoli) and Pichia pastoris recombinant LTPs (carrot and wheat) were included. Pepsin digestion was used to address the role of stability in the allergenicity of LTPs. Results: IgE antibodies to Rosaceae LTPs reacted to a broad range of vegetable foods, including Gramineae (cereals), Leguminosae (peanut), Juglandaceae (walnut), Anacardiaceae (pistachio), Brassicaceae (broccoli), Umbelliferae (carrot, celery), Solanaceae (tomato), Cucurbitaceae (melon), and Actinidiaceae (kiwi). Binding and inhibition studies with purified natural and recombinant LTPs confirmed their role in this cross-reactivity. Many of these cross-reactivities were accompanied by clinical food allergy, frequently including systemic reactions. Antibody binding to LTP was shown to be resistant to pepsin treatment of whole extract or purified LTP. Conclusion: LTP is a pan-allergen with a degree of cross-reactivity comparable to profilin. Due to its extreme resistance to pepsin digestion, LTP is a potentially severe food allergen.

Halmepuro L, Vuontela K, Kalimo K, Björksten F: Cross-reactivity of IgE antibodies with allergens in birch pollen, fruits and vegetables. Int Arch Allergy Appl Immunol 1984;74:235–240.
Lahti A, Björksten F, Hannuksela M: Allergy to birch pollen and apple, and cross-reactivity of the allergens studied with the RAST. Allergy 1980;35:297–300.
Ebner C, Birkner T, Valenta R, Rumpold H, Breitenbach M, Scheiner O, Kraft D: Common epitopes of birch pollen and apples – Studies by Western and Northern blot. J Allergy Clin Immunol 1991;88:588–594.
Ebner C, Hirschwehr R, Bauer L, Breiteneder H, Valenta R, Ebner H, Kraft D, Scheiner O: Identification of allergens in fruits and vegetables: IgE cross-reactivities with the important birch pollen allergens Bet v 1 and Bet v 2 (birch profilin). J Allergy Clin Immunol 1995;95:962–969.
Breiteneder H, Pettenburger K, Bito A, Valenta R, Kraft D, Rumpold H, Scheiner O, Breitenbach M: The gene coding for the major birch pollen allergen Bet v 1, is highly homologous to a pea disease resistance gene. EMBO J 1989;8:1935–1938.
Van Ree R, Aalberse RC: Pollen-vegetable food crossreactivity: Serologic and clinical relevance of crossreactive IgE. J Clin Immunoassay 1993;16:124–130.
Calkhoven PG, Aalbers M, Koshte V, Pos S, Oei HD, Aalberse RC: Cross-reactivity among birch pollen, vegetables and fruits as detected by IgE antibodies is due to at least three distinct cross-reactive structures. Allergy 1987;42:382–390.
Van Ree R: The oral allergy syndrome; in Amin S, Lahti A, Maibach HI (eds): Contact Urticaria Syndrome. Boca Raton, CRC Press, 1997, pp 289–299.
Björksten F, Halmepuro L, Hannuksela M, Lahti A: Extraction and properties of apple allergens. Allergy 1980;35:671–677.
Rudeschko O, Fahlbusch B, Henzgen M, Schlenvoigt G, Herrmann D, Vieths S, Jager L: Investigation of the stability of apple allergen extracts. Allergy 1995;50:575–580.
Rosen JP, Selcow JE, Mendelson LM, Grodofsky MP, Factor JM, Sampson HA: Skin testing with natural foods in patients suspected of having food allergies: Is it a necessity? [see comments]. J Allergy Clin Immunol 1994;93:1068–1070.
Ortolani C, Ispano M, Pastorello EA, Ansaloni R, Magri GC: Comparison of results of skin prick tests (with fresh foods and commercial food extracts) and RAST in 100 patients with oral allergy syndrome. J Allergy Clin Immunol 1989;83:683–690.
Rance F, Juchet A, Bremont F, Dutau G: Correlations between skin prick tests using commercial extracts and fresh foods, specific IgE, and food challenges. Allergy 1997;52:1031–1035.
Asero R, Massironi F, Minisini S, Venturini E, Velati C: Detection of a subgroup of fruit-sensitive patients with oral allergy syndrome by commercial food antigen extracts. Gior Ital Allergol Immunol Clin 1993;3:39–43.
Asero R: Detection and clinical characterization of patients with oral allergy syndrome caused by stable allergens in Rosaceae and nuts. Ann Allergy Asthma Immunol 1999;83:377–383.
Fernandez-Rivas M, Van Ree R, Cuevas M: Allergy to Rosaceae fruits without related pollinosis. J Allergy Clin Immunol 1997;100:728–733.
Pastorello EA, Ortolani C, Farioli L, Pravettoni V, Ispano M, Borga A, Bengtsson A, Incorvaia C, Berti C, Zanussi C: Allergenic cross-reactivity among peach, apricot, plum, and cherry in patients with oral allergy syndrome: An in vivo and in vitro study. J Allergy Clin Immunol 1994;94:699–707.
Pastorello EA, Farioli L, Pravettoni V, Ortolani C, Ispano M, Monza M, Baroglio C, Scibola E, Ansaloni R, Incorvaia C, Conti A: The major allergen of peach (Prunus persica) is a lipid transfer protein. J Allergy Clin Immunol 1999;103:520–526.
Sanchez-Monge R, Lombardero M, Garcia-Selles FJ, Barber D, Salcedo G: Lipid-transfer proteins are relevant allergens in fruit allergy. J Allergy Clin Immunol 1999;103:514–519.
Lleonart R, Cistero A, Carreira J, Batista A, Moscoso DP: Food allergy: Identification of the major IgE-binding component of peach (Prunus persica). Ann Allergy 1992;69:128–130.
Arondel V, Kader JC: Lipid transfer in plants. Experientia 1990;46:579–585.
Rueckert DG, Schmidt K: Lipid transfer proteins. Chem Phys Lipids 1990;56:1–20.
Wirtz KW: Phospholipid transfer proteins revisited. Biochem J 1997;324(pt 2):353–360.
Pyee J, Yu H, Kolattukudy PE: Identification of a lipid transfer protein as the major protein in the surface wax of broccoli (Brassica oleracea) leaves. Arch Biochem Biophys 1994;311:460–468.
Poznanski J, Sodano P, Suh SW, Lee JY, Ptak M, Vovelle F: Solution structure of a lipid transfer protein extracted from rice seeds. Comparison with homologous proteins. Eur J Biochem 1999;259:692–708.
Lerche MH, Poulsen FM: Solution structure of barley lipid transfer protein complexed with palmitate. Two different binding modes of palmitate in the homologous maize and barley nonspecific lipid transfer proteins. Protein Sci 1998;7:2490–2498.
Lerche MH, Kragelund BB, Bech LM, Poulsen FM: Barley lipid-transfer protein complexed with palmitoyl CoA: The structure reveals a hydrophobic binding site that can expand to fit both large and small lipid-like ligands. Structrue 1997;5:291–306.
Gomar J, Sodano P, Sy D, Shin DH, Lee JY, Suh SW, Marion D, Vovelle F, Ptak M: Comparison of solution and crystal structures of maize nonspecific lipid transfer protein: a model for a potential in vivo lipid carrier protein. Proteins 1998;31:160–171.
Tassin S, Broekaert WF, Marion D, Acland DP, Ptak M, Vovelle F, Sodano P: Solution structure of Ace-AMP1, a potent antimicrobial protein extracted from onion seeds. Structural analogies with plant nonspecific lipid transfer proteins. Biochemistry 1998;37:3623–3637.
Lee JY, Min K, Cha H, Shin DH, Hwang KY, Suh SW: Rice non-specific lipid transfer protein: The 1.6 A crystal structure in the unliganded state reveals a small hydrophobic cavity. J Mol Biol 1998;276:437–448.
Shin DH, Lee JY, Hwang KY, Kim KK, Suh SW: High-resolution crystal structure of the non-specific lipid-transfer protein from maize seedlings. Structure 1995;3:189–199.
Gincel E, Simorre JP, Caille A, Marion D, Ptak M, Vovelle F: 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 1994;226:413–422.
Garcia-Olmedo F, Molina A, Segura A, Moreno M: The defensive role of nonspecific lipid-transfer proteins in plants. Trends Microbiol 1995;3:72–74.
Segura A, Moreno M, Garcia-Olmedo F: Purification and antipathogenic activity of lipid transfer proteins (LTPs) from the leaves of Arabidopsis and spinach. FEBS Lett 1993;332:243–246.
Molina A, Segura A, Garcia-Olmedo F: Lipid transfer proteins (nsLTPs) from barley and maize leaves are potent inhibitors of bacterial and fungal plant pathogens. FEBS Lett 1993;316:119–122.
Molina A, Garcia-Olmedo F: Enhanced tolerance to bacterial pathogens caused by the transgenic expression of barley lipid transfer protein LTP2. Plant J 1997;12:669–675.
Nielsen KK, Nielsen JE, Madrid SM, Mikkelsen JD: New antifungal proteins from sugar beet (Beta vulgaris L.) showing homology to non-specific lipid transfer proteins. Plant Mol Biol 1996;31:539–552.
Cammue BP, Thevissen K, Hendriks M, Eggermont K, Goderis IJ, Proost P, Van Damme J, Osborn RW, Guerbette F, Kader JC: A potent antimicrobial protein from onion seeds showing sequence homology to plant lipid transfer proteins. Plant Physiol 1995;109:445–455.
Torres-Schumann S, Godoy JA, Pintor-Toro JA: A probable lipid transfer protein gene is induced by NaCl in stems of tomato plants. Plant Mol Biol 1992;18:749–757.
Ostergaard J, Hojrup P, Knudsen J: Amino acid sequences of three acyl-binding/lipid-transfer proteins from rape seedlings. Biochim Biophys Acta 1995;1254:169–179.
Meijer EA, De Vries SC, Sterk P, Gadella DWJ, Wirtz KW, Hendriks T: Characterization of the non-specific lipid transfer protein EP2 from carrot (Daucus carota L.). Mol Cell Biochem 1993;123:159–166.
Sterk P, Booij H, Schellekens GA, Van Kammen A, De Vries SC: Cell-specific expression of the carrot EP2 lipid transfer protein gene. Plant Cell 1991;3:907–921.
Striver K, Leah R, Muller-Uri F, Olsen FL, Mundy J: Structure and expression of the barley lipid transfer protein gene Ltp1. Plant Mol Biol 1992;18:585–589.
Dieryck W, Gautier MF, Lullien V, Joudrier P: Nucleotide sequence of a cDNA encoding a lipid transfer protein from wheat (Triticum durum Desf.). Plant Mol Biol 1992;19:707–709.
Vignols F, Lund G, Pammi S, Tremousaygue D, Grellet F, Kader JC, Puigdomenech P, Delseny M: Characterization of a rice gene coding for a lipid transfer protein. Gene 1994;142:265–270.
Pelese-Siebenbourg F, Caelles C, Kader JC, Delseny M, Puigdomenech P: A pair of genes coding for lipid-transfer proteins in Sorghum vulgare. Gene 1994;148:305–308.
Coutos-Thevenot P, Jouenne T, Maes O, Guerbette F, Grosbois M. Le Caer JP, Boulay M, Deloire A, Kader JC, Guern J: Four 9-kDa proteins excreted by somatic embryos of grapevine are isoforms of lipid-transfer proteins. Eur J Biochem 1993;217:885–889.
Bousquet J, Michel FB: In vivo methods for the study of allergy: skin tests, techniques and interpretation; in Middleton E, Reed CE, Ellis EF, Adkinson NF, Yunginger JW, Busse WW (eds): Allergy: Principles and Practice. St Louis, Mosby, 1993, pp 573–594.
Akkerdaas JH, Van Ree R, Aalbers M, Stapel SO, Aalberse RC: Multiplicity of cross-reactive epitopes on Bet v I as detected with monoclonal antibodies and human IgE. Allergy 1995;50:215–220.
Lindberg U, Schutt CE, Hellsten E, Tjäder A-C, Hult T: The use of poly(L-proline)-Sepharose in the isolation of profilin and profilactin complexes. Biochim Biophys Acta 1988;967:391–400.
Van Ree R, Van Leeuwen WA, Akkerdaas JH, Aalberse RC: How far can we simplify in vitro diagnostics for Fagales tree pollen allergy? A study with three whole pollen extracts and purified natural and recombinant allergens. Clin Exp Allergy 1999;29:848–855.
Van Ree R, Hoffman DR, Van Dijk W, Brodard V, Mahieu K, Koeleman CA, Grande M, Van Leeuwen WA, Aalberse RC: Lol p 11, a new major grass pollen allergen, is a member of a family of soybean trypsin inhibitor-related proteins. J Allergy Clin Immunol 1995;95:970–978.
Klein C, de Lamotte-Guery F, Gautier F, Moulin G, Boze H, Joudrier P, Gautier MF: High-level secretion of a wheat lipid transfer protein in Pichia pastoris. Protein Expr Purif 1998;13:73–82.
Aalberse RC, Koshte V, Clemens JGJ: Immunoglobulin E antibodies that crossreact with vegetable foods, pollen and Hymenoptera venom. J Allergy Clin Immunol 1981;68:356–364.
Schuurman J, Perdok GJ, Lourens TE, Parren PW, Chapman MD, Aalberse RC: Production of a mouse/human chimeric IgE monoclonal antibody to the house dust mite allergen Der p 2 and its use for the absolute quantification of allergen-specific IgE. J Allergy Clin Immunol 1997;99:545–550.
Van Ree R, Van Leeuwen WA, Van den Berg M, Weller HH, Aalberse RC: IgE and IgG cross-reactivity among Lol p 1 and Lol p 2/3. Identification of the C-termini of Lol p 1, 2, and 3 as cross-reactive structures. Allergy 1994;49:254–261.
Van Ree R, Akkerdaas J, Van Leeuwen A, Fernandez-Rivas M, Asero R, Knul-Brettlova V, Knulst A, Aalberse RC: New perspectives for the diagnosis of food allergy. Allergy Clin Immunol Int 2000;12:7–12.
Valenta R, Duchêne M, Ebner C, Valent P, Sillaber C, Deviller P, Ferreira F, Tejkl M, Edelmann H, Kraft D, Scheiner O: Profilins constitute a novel family of functional plant pan-allergens. J Exp Med 1992;175:377–385.
Van Ree R, Voitenko V, Van Leeuwen WA, Aalberse RC: Profilin is a cross-reactive allergen in pollen and vegetable foods. Int Arch Allergy Immunol 1992;98:97–104.
Van Ree R, Fernandez-Rivas M, Cuevas M, Van Wijngaarden M, Aalberse RC: Pollen-related allergy to peach and apple: An important role for profilin. J Allergy Clin Immunol 1995;95:726–734.
Valenta R, Kraft D: Type I allergic reactions to plant-derived food: A consequence of primary sensitization to pollen allergens. J Allergy Clin Immunol 1996;97:893–895.
Colombo P, Duro G, Costa MA, Izzo V, Mirisola M, Locorotondo G, Cocchiara R, Geraci D: An update on allergens. Parietaria pollen allergens. Allergy 1998;53:917–921.
Duro G, Colombo P, Assunta CM, Izzo V, Porcasi R, Di Fiore R, Locorotondo G, Cocchiara R, Geraci D: Isolation and characterization of two cDNA clones coding for isoforms of the Parietaria judaica major allergen Par j 1.0101. Int Arch Allergy Immunol 1997;112:348–355.
Duro G, Colombo P, Costa MA, Izzo V, Porcasi R, Di Fiore R, Locorotondo G, Mirisola MG, Cocchiara R, Geraci D: cDNA cloning, sequence analysis and allergological characterization of Par j 2.0101, a new major allergen of the Parietaria judaica pollen. FEBS Lett 1996;399:295–298.
Costa MA, Colombo P, Izzo V, Kennedy H, Venturella S, Cocchiara R, Mistrello G, Falagiani P, Geraci D: cDNA cloning, expression and primary structure of Par j I, a major allergen of Parietaria judaica pollen. FEBS Lett 1994;341:182–186.
Inschlag C, Hoffmann-Sommergruber K, O’Riordain G, Ahorn H, Ebner C, Scheiner O, Breiteneder H: Biochemical characterization of Pru a 2, a 23-kD thaumatin-like protein representing a potential major allergen in cherry (Prunus avium). Int Arch Allergy Immunol 1998;116:22–28.
Higginbotham JD, Snodin DJ, Eaton KK, Daniel JW: Safety evaluation of thaumatin (Talin protein). Food Chem Toxicol 1983;21:815–823.
Blanco C, Diaz-Perales A, Collada C, Sanchez-Monge R, Aragoncillo C, Castillo R, Ortega N, Alvarez M, Carrillo T, Salcedo G: Class I chitinases as potential panallergens involved in the latex-fruit syndrome. J Allergy Clin Immunol 1999;103:507–513.
Sowka S, Hsieh LS, Krebitz M, Akasawa A, Martin BM, Starrett D, Peterbauer CK, Scheiner O, Breiteneder H: Identification and cloning of Prs a 1, a 32-kDa endochitinase and major allergen of avocado, and its expression in the yeast Pichia pastoris. J Biol Chem 1998;273:28091–28097.
Diaz-Perales A, Collada C, Blanco C, Sanchez-Monge R, Carrillo T, Aragoncillo C, Salcedo G: Class I chitinases with hevein-like domain, but not class II enzymes, are relevant chestnut and avocado allergens. J Allergy Clin Immunol 1998;102:127–133.
Pastorello EA, Farioli L, Pravettoni V, Ispano M, Conti A, Ansaloni R, Rotondo F, Incorvaia C, Bengtsson A, Rivolta F, Trambaioli C, Previdi M, Ortolani C: Sensitization to the major allergen of Brazil nut is correlated with the clinical expression of allergy. J Allergy Clin Immunol 1998;102:1021–1027.
Teuber SS, Dandekar AM, Peterson WR, Sellers CL: Cloning and sequencing of a gene encoding a 2S albumin seed storage protein precursor from English walnut (Juglans regia), a major food allergen. J Allergy Clin Immunol 1998;101:807–814.
Gonzalez De La Pena MA, Monsalve RI, Batanero E, Villalba M, Rodriguez R: Expression in Escherichia coli of Sin a 1, the major allergen from mustard. Eur J Biochem 1996;237:827–832.
Astwood JD, Leach JN, Fuchs RL: Stability of food allergens to digestion in vitro. Nat Biotechnol 1996;14:1269–1273.
Becker WM: Characterization of Ara h 1 by two-dimensional electrophoresis immunoblot and recombinant techniques: new digestion experiments with peanuts imitating the gastrointestinal tract. Int Arch Allergy Immunol 1997;113:118–121.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.