High risk of asthma among early teens is associated with quantitative differences in mite and cat allergen specific IgE and IgG4: a modified Th2 related antibody response revisited.

Background: Although proteins derived from cats are an important contributor to indoor allergen exposure in relation to asthma, it has been known for at least twenty years that some children who live in a house with a cat can become clinically tolerant to these animals. In 2001, we reported that children exposed to high levels of cat allergens made high levels of IgG4 antibodies to the cat allergen Fel d 1, and we coined the term "a modified Th2 response". However, this phenomenon is still poorly understood.

Methods: We studied serum antibodies among 616 individuals in the Viva unselected birth cohort recruited at their early teen visit (mean age 13.1 SD 0.8). IgE and IgG4 antibodies were measured by ImmunoCAP to inhaled allergens as well as the best characterised component allergens of cat, Fel d 1, Fel d 2, Fel d 4, and Fel d 7, and the dust mite allergens Der p 1, Der p 2, Der p 10, and Der p 23.

Findings: The results confirm that young teens living in a home with a cat make high levels of IgG4 specific for cat allergens, and that those antibodies, and specifically those to Fel d 1 are negatively associated with asthma. By contrast, the IgG4 responses to Fel d 4 and Fel d 7 are significantly lower and have no significant association with asthma. Perhaps more surprisingly, a similar effect is seen in relation to dust-mite allergens. Although the allergen Der p 1 is a major part of the IgE response to mite allergens, this protein also induced high prevalence and levels of IgG4 antibodies and has a less strong relationship to asthma than IgE to Der p 2 or Der p 23. Indeed, values of specific IgE to Der p 1 >3.5 IU/mL were not significantly related to asthma (OR 1.5 CI 0.8-2.8, p = 0.3, Chi² test). The prevalence and levels of specific IgG4 to these less abundant allergens are significantly lower for Der p 2 and almost absent for Der p 23.

Interpretation: High exposure to specific allergens in household dust can enhance production of both sIgE and sIgG4 antibodies, while allergens where abundance is significantly lower in dust can induce sIgE with limited or no sIgG4. The result is that the less abundant allergens, i.e., Fel d 4, Fel d 7, Der p 2, and Der p 23, may have a significantly higher relevance to asthma than expected because they induce less sIgG4.

Funding: This work was funded by R01-AI20565 (TPM) and support for the IgE and IgG4 assays provided by Phadia/Thermo Fisher Kalamazoo, Michigan. Project Viva is also supported by NIH R01HD034568 and R24ES.