Diminished allergic disease in patients with STAT3 mutations points to role for STAT3 signaling in mast cell degranulation

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NIAID	IMMUNO-20

Authors

• A.M. Siegel
• K.D. Stone
• M.G. Lawrence
• M. Jung
• J. Barber
• A.F. Freeman
• S.M. Holland
• M. O'Brien
• N. Jones
• L. Wisch
• A. Desai
• A. Gilfillan
• J.D. Milner

Abstract

One third of patients with severe atopic dermatitis have food allergies – six times higher than the average incidence of allergic disease among the general public. Patients with autosomal dominant hyper-IgE syndrome (AD-HIES) due to dominant negative STAT3 mutations have a spectrum of phenotypes including atopic dermatitis and high levels of serum IgE, yet their susceptibility to specific allergic disease has not been examined. We obtained allergic histories in 39 healthy volunteers, 78 AD-HIES patients, and 66 patients with severe atopy but no STAT3 mutations. AD-HIES patients had a lower incidence of food allergies as compared to atopic controls. Fewer STAT3-mutant patients had anaphylaxis to food allergens than atopic controls. We observed high levels of specific IgE to many food and aeroallergens in the serum of AD-HIES patients. Responses to morphine skin prick testing, which measures mast cell degranulation independent of IgE, were diminished in AD-HIES patients compared to healthy controls. Knockdown of STAT3 in a human mast cell line significantly impaired mast cell degranulation. Alterations in the STAT3 signaling pathway may impact mast cell biology leading to paradoxical protection from atopy in patients with marked elevations of IgE.

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