Pathogenesis and Treatment of Atopic Dermatitis

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

This is the first report for this project. We have begun to assemble a cohort of patients with atopic dermatitis alone, and those with AD in the context of immune deficiency-- a patient group whose comorbid immunodeficiency may help point towards the pathophysiology underlying the atopic dermatitis. Concurrently, we have begun to develop screening assays for a number of pathways predicted to be disrupted in atopic dermatitis. These include TCR signaling, TCR repertoire and STAT3 axis disruptions. We also are in the process of submitting a dedicated protocol for studying the natural history and management of atopic dermatitis, and another for the treatment of severe refractory atopic dermatitis with anakinra, the IL-1 receptor antagonist. Additionally, we have been able to study the role of STAT3 in lymphocyte homeostasis, since STAT3 disruption leads to elevated IgE and atopic dermatitis in the Hyper-IgE syndrome. A patient with STAT3 mosaicism was identified in collaboration with Steve Holland's group, and by sorting lymphocyte populations and sequencing for the mutant, we have been able to establish the relative contribution of the mutant allele to T- and B-intrinsic defects seen in HIES. These defects may have specific roles in the pathogenesis of the atopic aspect of HIES, and therefore have broader implications for atopic disease in general.