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 Feld1, and we coined the term "a modified Th2 response". However, this phenomenon is still poorly understood. 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, Feld1, Feld2, Feld4, and Feld7, and the dust mite allergens Derp1, Derp2, Derp10, and Derp23. 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 Feld1 are negatively associated with asthma. By contrast, the IgG4 responses to Feld4 and Feld7 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 Derp1 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 Derp2 or Derp23. Indeed, values of specific IgE to Derp1 >3.5IU/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 Derp2 and almost absent for Derp23. 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., Feld4, Feld7, Derp2, and Derp23, may have a significantly higher relevance to asthma than expected because they induce less sIgG4. 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.
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