Serum cytotoxic T lymphocyte-associated antigen 4 in hymenoptera venom allergy and its modulation by specific immunotherapy

BACKGROUND: Cytotoxic T lymphocyte associated gene-4 (CTLA-4) is now recognized as a negative regulatory factor for activated lymphocytes, and may be therefore involved in the pathogenic mechanismof allergies. We assessed the levels of the soluble form of CTLA-4 molecule in subjects with a pure IgE mediated disease, hymenoptera venom allergy, and its modulation by immunotherapy. Thirty patients with grade III-IV reactions, sensitized to hymenoptera only, and receiving specific immunotherapy were enrolled. Serum CTLA-4 and Interleukin-10 were assayed in the serum at baseline and after the 6-week induction phase of immunotherapy. Specific IgE and IgG4 were also measured, Serum CTLA-4 was also measured in 27 patients with allergic rhinitis, as well as in 45 healthy subjects. ELISA methods and Western blotting were used. Serum CTLA-4was undetectable in almost all healthy controls and rhinitis patients, whereas it was raised in hymenoptera venom patients (median 17.5 range 0.1-95 ng/mL). Its concentration significantly decreased after immunotherapy induction (median 3.3, range 0.1-34.5 ng/mL; p 5 0.0004), in parallel with a significant increase in interleukin- 10 (p50.0001). No change at all was seen in IgE and IgG4 concentrations. Soluble CTLA-4 in serum clearly discriminates the subjects with hymenoptera allergy from those with respiratory allergy and normals. In addition it may represent an early marker of the immunological effects of specific immunotherapy.