COMBINED NASAL CHALLENGE WITH DIESEL EXHAUST PARTICLES AND ALLERGEN INDUCES IN-VIVO IGE ISOTYPE SWITCHING

In this study we undertook to provide evidence for local in vivo isoty pe switching to IgE following nasal challenges, Detection of deleted s witch circular DNA (switch circles) by a novel nested polymerase chain reaction-based approach was employed as definitive molecular evidence of Ig isotype switching. Nasal challenge in humans with diesel exhaus t particles (DEP) plus ragweed antigen has been shown to enhance local IgE production, stimulate local cytokine production, and markedly inc rease mucosal IgE antibody to ragweed. Four days after combined intran asal DEP plus ragweed challenge, we detected and characterized clones of deleted switch circular DNA (S epsilon/S mu) representing switching from mu to epsilon from nasal lavage cells. No switch circular DNA wa s detected in nasal lavage cells following challenge with DEP alone no r with ragweed allergen alone. These results indicate that the combina tion of mucosal stimulation with DEP and ragweed allergen is capable o f driving in vivo isotype switching to IgE in humans with ragweed alle rgy. These results are the first direct demonstration of in vivo IgE i sotype switching in humans.