Grass pollen injection immunotherapy (IT) is associated with a suppressive response mediated by IL-10 and TGF-β, inducing respectively IgG4 and IgA production. We assessed the IgA response in patients with severe seasonal rhinitis during a double-blind, placebo-controlled trial of grass pollen IT, and related the findings to TGF-β expression in the nasal mucosa.

Serum concentrations of IgA1, IgA2 and joining chain-containing IgA antibodies to grass pollen (GP extract or Phl p 5) were measured by ELISA using specific monoclonal antibodies (and expressed as arbitrary units) before treatment and after 2 years of IT. TGF-β mRNA was assessed by in situ hybridization in nasal biopsies taken before and after 2 year IT.

Serum IgA2 antibodies to GP were significantly increased after 2 years of IT as compared with placebo (median: 35.65, IQ range: 29.4-49.9 versus 8.15, 1-17.78, p<0.0001, Mann-Whitney U-test), as also observed for IgA2 to Phl p 5. In contrast, IgA1 antibodies to GP were increased to a much lower extent and only at the peak pollen season. Mucosal-derived, joining chain-containing IgA to Phl p 5 was significantly increased after 2 years of IT as compared with placebo (108, 94.11-151.33 versus 80.22, 54.39-116.47, p=0.02). Moreover, levels of serum IgA2 antibodies to Phl p 5 significantly correlated with TGF-β expression in the nasal mucosa (p=0.01, r=0.60).

The IgA response to grass pollen immunotherapy is mostly of the IgA2 subclass, and grass pollen-specific serum IgA2 antibodies could be, at least partly, produced within the nasal mucosa and associated with local TGF-β expression.