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Dictionary of Allergies .. Bee venom immunotherapy

Venom immunotherapy (VIT) for bee venom allergy is proven to be curative for insect allergy and provides long-term protection[1], but the mechanisms and the biomarkers associated with clinical efficacy remain elusive. We report herein the discovery of a leading candidate biomarker, osteopontin (OPN), for VIT. From cDNA microarray and clustering analyses, an increased expression of OPN was found in patients who completed 5-6 years of VIT and discontinued therapy for 3-6 years as compared with the untreated group. A significantly higher level of serum OPN was found in the completed treatment group as compared with the untreated group. Following VIT, kinetically increased levels of OPN associated with reduced venom specific IgE levels were noted in subjects with large local allergic reactions to venom. These findings together with the fact that OPN is involved in Th1-associated immune response strongly suggest a role of OPN as a functional biomarker for VIT [2]. 

Venom-specific IgG4 levels are increased but with no correlation with clinical improvement. In contrast to grass pollen immunotherapy, the persistent decline in venom-specific IgE levels, rather than serum inhibitory activity for facilitated-allergen binding (FAB) assay , may be more relevant for long-term clinical efficacy of VIT[1]. 

Double positivity of IgE to bee and Vespula venom is often caused by crossreactions, especially to CCDs. IgE to both Api m1 and Ves v5 indicates true double sensitization and immunotherapy with both venoms[3].

H1 antihistamines increase safety during allergen-specific immunotherapy and might influence the outcome because of immunoregulatory effects[4]. Levocetirizine (LC) reduces side effects during dose increase without influencing the efficacy of ultrarush honeybee venom immunotherapy. LC modulates the natural course of allergen-specific immune response and affects the expression of histamine receptors and cytokine production by allergen-specific T cells [4].

Venom immunotherapy (VIT) is the only effective treatment for prevention of serious allergic reactions to bee and wasp stings in sensitized individuals[5].

Sublingual immunotherapy with venom is not recommended for patients with Hymenoptera venom allergy[6].


1. Varga EM, Francis JN, Zach MS, Klunker S, Aberer W, Durham SR. Time course of serum inhibitory activity for facilitated allergen-IgE binding during bee venom immunotherapy in children. Clin Exp Allergy. 2009 Jun 15. 

2. Konno S, Hizawa N, Nishimura M, Huang SK. Osteopontin: a potential biomarker for successful bee venom immunotherapy and a potential molecule for inhibiting IgE-mediated allergic responses. Allergol Int. 2006 Dec;55(4):355-9.

3. Müller UR, Johansen N, Petersen AB, Fromberg-Nielsen J, Haeberli G. Hymenoptera venom allergy: analysis of double positivity to honey bee and Vespula venom by estimation of IgE antibodies to species-specific major allergens Api m1 and Ves v5. Allergy. 2009 Apr;64(4):543-8.

4. Müller UR, Jutel M, Reimers A, Zumkehr J, Huber C, Kriegel C, Steiner U, Haeberli G, Akdis M, Helbling A, Schnyder B, Blaser K, Akdis C. Clinical and immunologic effects of H1 antihistamine preventive medication during honeybee venom immunotherapy. J Allergy Clin Immunol. 2008 Nov;122(5):1001-1007.e4. Epub 2008 Oct 9.

5. Diwakar L, Noorani S, Huissoon AP, Frew AJ, Krishna MT. Practice of venom immunotherapy in the United Kingdom: a national audit and review of literature. Clin Exp Allergy. 2008 Oct;38(10):1651-8. Comment in:Clin Exp Allergy. 2008 Oct;38(10):1576-8.

6. Ruëff F, Bilò MB, Jutel M, Mosbech H, Müller U, Przybilla B; Interest group on Hymenoptera venom allergy of the European Academy of Allergology and Clinical Immunology. Sublingual immunotherapy with venom is not recommended for patients with Hymenoptera venom allergy. J Allergy Clin Immunol. 2009 Jan;123(1):272-3; author reply 273 Comment on:J Allergy Clin Immunol. 2008 Jul;122(1):44-8.

Γκέλης Ν.Δ. - Λεξικό Αλλεργίας - Εκδόσεις ΒΕΛΛΕΡOΦΟΝΤΗΣ - Κόρινθος 2013

Gelis Ν.D. - Dictionary of Allergies - VELLEROFONTIS Publications - Corinth 2013