Evaluation of serum IgG4 antibodies specific to grass pollen allergen components in the follow up of allergic patients undergoing subcutaneous and sublingual immunotherapy.

BACKGROUND: A number of reports suggest that induction of IgG 'blocking antibodies' may be important for successful allergen immunotherapy. Nevertheless, a significant increase in specific IgG and IgG4 antibodies has not been consistently demonstrated for sublingual immunotherapy (SLIT).
METHODS: The present observation included three groups of grass pollen allergic patients all submitted to three different allergen immunotherapeutic regimens in an open, non-placebo controlled clinical study: (i) 16 patients underwent a modified 'cluster' regimen of weekly injections of a standardized aluminium-absorbed Phleum pratense extract for 5 weeks, followed by 3 weeks of maintenance injections. (ii) Fifteen patients were treated with standardized timothy grass pollen-allergen oral vaccine. In the first session of a SLIT protocol without up-dosing, each patient received 2.4 ml of sublingual vaccine containing about 57 microg of Phl p 5 and received a maintenance dose of 24 microg of Phl p 5 once a day for 120 days. (iii) Fourteen subjects were treated with a standardized allergen extract containing 5-grass pollen mixture; a SLIT protocol was performed without up-dosing, administering a dose corresponding to about 10.0 microg/ml grass-pollen Group 5 and a maintenance dose of 4 microg of grass-pollen Group 5 once a day for 135 days. Patients' sera were characterized in detail by determining IgG4 antibodies to rPhl p 1, 2, 5, 6, 7, 11, 12 and nPhl p 4 and eosinophil cationic protein before the start of immunotherapy and during the peak of pollen season.
RESULTS: No relevant systemic side effects were registered in patients treated with the modified cluster subcutaneous immunotherapy (SCIT) protocol and the two SLIT protocols without build-up phase. After SCIT all patients had high titres of serum allergen-specific IgG4 antibodies. High-dose SLIT led to an IgG4 increase comprising 25% of the SCIT level, while low-dose SLIT increased to 4% of the SCIT. Furthermore, the increase of specific IgG antibodies corresponds to a decrease of serum ECP during allergen exposure.
CONCLUSIONS: These preliminary data seem to indicate that: (i) pre-seasonal high-dose SLIT protocol without build-up phase is safe and well-tolerated by allergic patients; (ii) compared to IgG4 levels induced by SCIT, only a high-dose SLIT regimen results in an appreciable serum specific IgG4 increase.