The location of IgE switching and IgE production in the target organ in allergy remains an unresolved question. We have investigated this problem in patients with hay fever compared with non-allergic controls.

PCR-based methodology was used to analyze different molecular markers closely associated with ongoing class switch recombination (CSR), germline transcripts (GLT), switch circle transcripts (CT) and activation-induced cytidine deaminase (AID) expression within the nasal mucosa of biopsies taken from grass pollen (GP)–sensitive-patients in-season, out-of-season and from non-allergic normal controls.

AID mRNA was detected in biopsies from 9/12 GP-sensitive patients. γ1, γ3 and γ4 GLTs were identified in 4/6 in-season and 5/6 out-of-season hay fever patients. In contrast, μ and ε GLTs were more prevalent in-season (5/6 and 6/6 patients, respectively) than out-of-season (both in 1/6 patients). Switch circle transcripts (Iε-Cγ1 and/or Iε-Cγ3) were observed in 4/6 biopsies from in-season and 1/6 biopsies from out-of-season patients. None of the three molecular markers were detected in nasal biopsies from non-allergic controls.

For the first time we have demonstrated 1) AID mRNA 2) μ and γ, in addition to εGLT and 3) switch circle transcripts (IεCγ1 and Iε-Cγ3) in the nasal mucosa in hay fever. The presence of CTs containing both ε and γ sequences provides definitive proof that switch recombination may occur locally in the target organ and further that switching may occur sequentially in the mucosa from μ to ε via γ. The findings support the development of strategies that target local switching as therapy for allergic disease.