There is no detailed comparison of allergen-specific immunoglobulin responses following sublingual (SLIT) and subcutaneous (SCIT) immunotherapy.

To compare nasal and systemic Timothy grass pollen (TGP)-specific antibody responses during two years of SCIT and SLIT and one year after treatment discontinuation in a double-blind, double-dummy, placebo-controlled trial.

Nasal fluid and serum were obtained yearly (per-protocol population, n=84). TGP-specific IgA1, IgA2, IgG4, IgG and IgE were measured in nasal fluids by ELISA. TGP-specific IgA1, IgA2 and Phl p1, 2, 4, 5b, 6, 7, 11 and 12 IgE and IgG4 were measured in sera by ELISA and ImmunoCAP, respectively.

At years 2 and 3, TGP-IgA1/2 in nasal fluid were elevated in SLIT compared to SCIT (4.2 and 3.0-fold for IgA1, 2.0 and 1.8-fold for IgA2, respectively; all P<.01). TGP-IgA1 in serum was elevated in SLIT compared to SCIT at years 1, 2, and 3 (4.6, 5.1, and 4.7-fold, respectively; all P<.001). Serum TGP-IgG was higher in SCIT compared to SLIT (2.8-fold) at year 2. Serum TGP-IgG4 was higher in SCIT compared to SLIT at years 1, 2, and 3 (10.4, 27.4, and 5.1-fold, respectively; all P<.01). Serum IgG4 to Phl p1, 2, 5b and 6 were increased at years 1, 2 and 3 in SCIT and SLIT compared to placebo (Phl p1: 11.8 and 3.9-fold; Phl p2: 31.6 and 4.4-fold; Phl p5b: 135.5 and 5.3-fold; Phl p6: 145.4 and 14.7-fold, respectively, all at year 2 when levels peaked; P<.05). IgE to TGP in nasal fluid increased in the SLIT group at year 2 but not year 3 compared to SCIT (2.8-fold; P=.04) and placebo (3.1-fold; P=.02). IgA to TGP and IgE and IgG4 to TGP-components stratified participants according to treatment group and clinical response.

The observed induction of IgA1/2 in SLIT and IgG4 in SCIT suggest key differences in the mechanisms of action.