Platts-Mills Thomas A, Keshavarz Behnam, Wilson Jeffrey M, Rifas-Shiman Sheryl L, Ailsworth Samuel M, Sordillo Joanne E, Workman Lisa, Chapman Martin, Lidholm Jonas, Oken Emily, Gold Diane R
Division of Allergy & Clinical Immunology, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
Division of Allergy & Clinical Immunology, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
EBioMedicine. 2025 Feb;112:105556. doi: 10.1016/j.ebiom.2024.105556. Epub 2025 Feb 1.
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.
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.
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, Chi 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.
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.
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.
尽管猫源蛋白是室内过敏原暴露导致哮喘的一个重要因素，但至少在二十年前就已知道，一些与猫同处一室的儿童在临床上可对这些动物产生耐受。2001年，我们报告称，接触高水平猫过敏原的儿童会产生高水平的针对猫过敏原Fel d 1的IgG4抗体，我们创造了“一种改变的Th2反应”这一术语。然而，这一现象仍未得到充分理解。
我们在Viva未选择的出生队列中，对616名在青少年早期就诊（平均年龄13.1岁，标准差0.8）的个体进行了血清抗体研究。通过免疫化学发光法（ImmunoCAP）检测了针对吸入性过敏原以及猫的特征最明确的组分过敏原Fel d 1、Fel d 2、Fel d 4和Fel d 7，以及尘螨过敏原Der p 1、Der p 2、Der p 10和Der p 23的IgE和IgG4抗体。
结果证实，生活在有猫的家庭中的青少年会产生高水平的针对猫过敏原的IgG4抗体，并且这些抗体，尤其是针对Fel d 1的抗体，与哮喘呈负相关。相比之下，对Fel d 4和Fel d 7的IgG4反应明显较低，且与哮喘无显著关联。或许更令人惊讶的是，在尘螨过敏原方面也观察到了类似的效应。尽管过敏原Der p 1是对螨过敏原的IgE反应的主要部分，但这种蛋白也诱导了高患病率和高水平的IgG4抗体，并且与哮喘的关系不如IgE与Der p 2或Der p 23的关系紧密。事实上，针对Der p 1的特异性IgE值>3.5 IU/mL与哮喘无显著相关性（比值比1.5，置信区间0.8 - 2.8，p = 0.3，卡方检验）。针对这些含量较少的过敏原的特异性IgG4的患病率和水平，对于Der p 2显著较低，对于Der p 23几乎不存在。
家庭灰尘中高暴露于特定过敏原可增强sIgE和sIgG4抗体的产生，而灰尘中含量显著较低的过敏原可诱导产生有限或无sIgG4的sIgE。结果是，含量较少的过敏原，即Fel d 4、Fel d 7、Der p 2和Der p 23，可能与哮喘的相关性比预期的显著更高，因为它们诱导产生的sIgG4较少。
这项工作由R01 - AI20565（TPM）资助，Phadia/赛默飞世尔科技（密歇根州卡拉马祖）为IgE和IgG4检测提供了支持。Viva项目也得到了美国国立卫生研究院R01HD034568和R24ES的支持。
