Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in patients allergic to bee venom☆,☆☆,★,★★
Section snippets
Antigens and reagents
Whole BV for skin tests and BVIT (Pharmalgen) was obtained from ALK (Horsholm, Denmark), and natural (n)PLA was obtained from Boehringer (Mannheim, Germany). Recombinant (r)PLA was expressed and refolded as described previously.15 The three PLA peptides were synthesized by automated solid-phase synthesis, with subsequent high-performance liquid chromatography. For skin testing and PIT, allergens and peptides were dissolved in commercially available diluent (Pharmalgen, ALK). IL-2 was a gift
Clinical course
The five patients (numbers 1, 2, 3, 4, and 5) were subjected to PIT with an equimolar mixture of the three PLA peptides PLA PI, PII, and PIII, each expressing a single T-cell epitope. The results of PIT were compared with those of 10 patients receiving BVIT. The clinical course and the results of the provocation tests in patients receiving PIT are shown in Table III. During PIT, no local or systemic allergic symptoms or any other side effects were caused by the subcutaneously injected peptides
DISCUSSION
In this first study of PIT in BV allergy, we applied an equimolar mixture of three short peptides, each containing a T-cell epitope of the major BV allergen PLA. The total dose of peptides injected corresponded to a 40-times higher amount of PLA than normally applied in BVIT. This was possible because the peptides did not bind IgE antibodies, and the skin sensitivity to the peptides was at least 104 times lower than that to intact PLA. Successful PIT correlated with the induction of specific
Acknowledgements
We thank Dr. Sefik Alkan, Novartis, Basel for his assistance in determination of some cytokines.
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From aMedical Division, Zieglerspital, Bern; bSwiss Institute of Allergy and Asthma Research (SIAF), Davos; and cInstitute of Immunology and Allergology, Inselspital, Bern.
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Supported by the Swiss National Science Foundation (grant no. 31.39.177.93).
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Reprint requests: Kurt Blaser, PhD, Swiss Institute of Allergy and Asthma Research (SIAF), CH-7270 Davos, Switzerland.
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