Research ArticleALLERGY

TGFβ Receptor Mutations Impose a Strong Predisposition for Human Allergic Disease

Science Translational Medicine  24 Jul 2013:
Vol. 5, Issue 195, pp. 195ra94
DOI: 10.1126/scitranslmed.3006448

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Allergy Unveiled

Loeys-Dietz syndrome (LDS) is an autosomal dominant disorder closely related to Marfan syndrome caused by mutations in the genes encoding receptor subunits for transforming growth factor–β (TGFβ). Patients with LDS are predisposed to aortic aneurisms and other connective tissue disorders. Now, Frischmeyer-Guerrerio et al. report that patients with LDS are more likely to develop allergic diseases.

Allergy occurs when the immune system responds to normally harmless substances. The authors observed that LDS patients had elevated incidence of allergic diseases, including asthma, food allergy, eczema, allergic rhinitis, and eosinophilic gastrointestinal disease. These patients had elevated levels of immune responses thought to contribute to allergy, including allergen-specific IgE, eosinophilia, and TH2 cytokines. Because regulatory T cell (Treg) development is regulated by TGFβ, the authors then examined Treg number and function in these patients. They found that the frequency of Tregs was increased in LDS patients, but that these cells produced TH2 effector cytokines, and in vitro studies suggested that LDS mutations promote TH2 inflammation. What’s more, children with allergic disease, but not LDS, had similar changes in Treg number and function. These data suggest that altered TGFβ signaling could promote allergic disease and support testing for U.S. Food and Drug Administration–approved drugs that affect TGFβ for treating allergy.