Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in patients allergic to bee venom.
BACKGROUND
Specific immunotherapy with honeybee venom (BV) is highly effective, but allergic side effects can occur during treatment. Immunotherapy with peptides containing major T-cell epitopes of the relevant allergen or allergens provides an alternative strategy without these problems.


OBJECTIVE
The study investigates the immunologic mechanisms and clinical effects of immunotherapy with T-cell epitope peptides of the major BV allergen, the phospholipase A2 (PLA).


METHODS
Five patients with IgE-mediated systemic allergic reactions to bee stings were treated with a mixture of three T-cell epitope peptides of PLA. Ten patients allergic to BV receiving whole BV immunotherapy served as control subjects. Increasing doses of the peptide mixture, up to a maintenance dose of 100 microg, were administered subcutaneously within 2 months. The patients were then challenged with PLA and 1 week later with a bee sting. The cellular and humoral immune response was measured in vitro.


RESULTS
No allergic side effects were caused by the peptide immunotherapy, and all patients tolerated the challenge with PLA without systemic allergic symptoms. Two patients developed mild systemic allergic reactions after the bee sting challenge. After peptide immunotherapy, specific proliferative responses to PLA and the peptides in peripheral blood mononuclear cells were decreased in successfully treated patients. The production of TH2 and TH1 cytokines was inhibited, and B cells were not affected in their capacity to produce specific IgE and IgG4 antibodies. Their levels increased after allergen challenge in favor of IgG4.


CONCLUSIONS
Immunotherapy of BV allergy with short T-cell peptides of PLA induces epitope-specific anergy in peripheral T cells and changes the specific isotype ratio in a fashion similar to that of conventional immunotherapy in successfully treated patients.
Müller
U
U
Medical Division, Zieglerspital, Bern, Switzerland.
Akdis
C A
CA
Fricker
M
M
Akdis
M
M
Blesken
T
T
Bettens
F
F
Blaser
K
K
D000293:Adolescent; D000328:Adult; D001514:Bee Venoms / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology*; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D010741:Phospholipases A / Q000276:immunology* / Q000627:therapeutic use*; D054467:Phospholipases A2; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology*
D001514:Bee Venoms; D000939:Epitopes; D011948:Receptors, Antigen, T-Cell; D010741:Phospholipases A; D054467:Phospholipases A2