Original Paper Int Arch Allergy Immunol 2000;122:20–32 Lipid Transfer Protein: A Pan-Allergen in Plant-Derived Foods That Is Highly Resistant to Pepsin Digestion Riccardo Asero a Gianni Mistrello b Daniela Roncarolo b Sacco C. de Vries c Marie-Françoise Gautier d Caroline L.F. Ciurana e Eddy Verbeek e Tamimount Mohammadi e Vlasta Knul-Brettlova f Jaap H. Akkerdaas e Ingrid Bulder e Rob C. Aalberse e Ronald van Ree e a Ambulatorio di Allergologia, Ospedale Caduti Bollatesi, Bollate, b Lofarma SpA, Milan, Italy; c Department of Molecular Biology, Agricultural University of Wageningen, The Netherlands; d Unité de Biochimie et Biologie Moléculaire des Céréales, INRA, Montpellier, France; e Department of Allergy, CLB and Laboratory for Experimental and Clinical Immunology, Academic Medical Centre, University of Amsterdam, f Prinsengracht Hospital, Department of Allergology, Amsterdam, The Netherlands Received: November 8, 1999 Accepted after revision: February 9, 2000 Correspondence to: Dr. R. van Ree CLB, Dept. of Allergy Plesmanlaan 125 NL–1066 CX Amsterdam (The Netherlands) Tel. +31 20 5123 242, Fax +31 20 5123 170, E-Mail r_van_ree@clb.nl ABC Fax + 41 61 306 12 34 E-Mail karger@karger. ch www. karger.com © 2000 S. Karger AG, Basel 1018–2438/00/1221–0020$17.50/0 Accessible online at: www. karger.com/journals/iaa Key Words Food allergy W Cross-reactivity W Lipid transfer protein W Protein stability W Recombinant allergens Abstract Background: Lipid transfer proteins (LTPs) are small mol- ecules of approximately 10 kD that demonstrate high sta- bility. They have recently been identified as allergens in the Rosaceae subfamilies of the Prunoideae (peach, apri- cot, 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. Objec- tive: 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 Rosa- ceae 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 puri- fied natural LTPs (peach, carrot and broccoli) and Pichia pastoris recombinant LTPs (carrot and wheat) were in- cluded. Pepsin digestion was used to address the role of stability in the allergenicity of LTPs. Results: IgE anti- bodies to Rosaceae LTPs reacted to a broad range of veg- etable foods, including Gramineae (cereals), Legumino- sae (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 bind- ing 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 compara- ble to profilin. Due to its extreme resistance to pepsin digestion, LTP is a potentially severe food allergen. Copyright © 2000 S. Karger AG, Basel