Abstract

BackgroundCytotoxic T lymphocyte associated antigen-4 (CTLA-4) is involved in the activation pathways of T lymphocytes. It has been shown that the circulating form of CTLA-4 is elevated in patients with hymenoptera allergy and can be down regulated by immunotherapy.Objectiveto assess the effects on CTLA-4 of venom immunotherapy, given with different induction protocols: conventional (6 weeks), rush (3 days) or ultra rush (1 day).MethodsSera from patients with hymenoptera allergy were collected at baseline and at the end of the induction phase. CTLA-4 and IL-10 were assayed in the same samples. A subset of patients were assayed also after 12 months of VIT maintenance.ResultsNinety-four patients were studied. Of them, 50 underwent the conventional induction, 20 the rush and 24 the ultra-rush. Soluble CTLA-4 was detectable in all patients at baseline, and significantly decreased at the end of the induction, irrespective of its duration. Of note, a significant decrease of sCTLA-4 could be seen already at 24 hours. In parallel, IL-10 significantly increased at the end of the induction. At 12 months, sCTLA-4 remained low, whereas IL-10 returned to the baseline values.ConclusionsSerum CTLA4 is an early marker of the immunological effects of venom immunotherapy, and its changes persist after one year of maintenance treatment.

Highlights

  • Allergy is the clinical manifestation of the ‘‘atopic status’’ that is characterized by an abnormal IgE response to ubiquitous substances, including pollens, foods, drugs and venoms of stinging insects

  • Serum CTLA4 is an early marker of the immunological effects of venom immunotherapy, and its changes persist after one year of maintenance treatment

  • Many different signalling molecules intervene in the immune response, and an increasing interest is currently devoted to the activation pathways of T lymphocytes

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Summary

Introduction

Allergy is the clinical manifestation of the ‘‘atopic status’’ that is characterized by an abnormal IgE response to ubiquitous substances, including pollens, foods, drugs and venoms of stinging insects. When the contact with the offending allergen is occasional and isolated (e.g. hymenoptera venom allergy, HVA, or food allergy) a ‘‘pure’’ IgE-mediated reaction takes place. This is essentially characterized by the sudden release of mast cell derived mediators (mainly histamine), triggered by IgE. An effective T-cell activation requires a primary signal delivered by the antigenic peptide presented by major histocompatibility complex molecules and a non-specific signal (co-stimulation) mediated by the interaction of CD28 with B7 family members (CD80, CD86) expressed on antigen-presenting cells [3]. It has been shown that the circulating form of CTLA-4 is elevated in patients with hymenoptera allergy and can be down regulated by immunotherapy

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