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.
| Oh, Kyu-Seon; Gottschalk, Rachel A; Lounsbury, Nicolas W et al. (2018) Dual Roles for Ikaros in Regulation of Macrophage Chromatin State and Inflammatory Gene Expression. J Immunol 201:757-771 |
| Natarajan, Mukil; Hsu, Amy P; Weinreich, Michael A et al. (2018) Aspergillosis, eosinophilic esophagitis, and allergic rhinitis in signal transducer and activator of transcription 3 haploinsufficiency. J Allergy Clin Immunol 142:993-997.e3 |
| Lyons, Jonathan J; Milner, Joshua D (2018) Primary atopic disorders. J Exp Med 215:1009-1022 |
| Milner, Joshua D (2018) TCR Signaling Abnormalities in Human Th2-Associated Atopic Disease. Front Immunol 9:719 |
| Siegfried, Elaine C; Jaworski, Jennifer C; Eichenfield, Lawrence F et al. (2018) Developing drugs for treatment of atopic dermatitis in children (?3 months to <18 years of age): Draft guidance for industry. Pediatr Dermatol 35:303-322 |
| Dillen, Carly A; Pinsker, Bret L; Marusina, Alina I et al. (2018) Clonally expanded ?? T cells protect against Staphylococcus aureus skin reinfection. J Clin Invest 128:1026-1042 |
| Zhang, Yuan; Ma, Chi A; Lawrence, Monica G et al. (2017) PD-L1 up-regulation restrains Th17 cell differentiation inSTAT3loss- andSTAT1gain-of-function patients. J Exp Med 214:2523-2533 |
| Gaudinski, Martin Robert; Milner, Joshua D (2017) Atopic Dermatitis and Allergic Urticaria: Cutaneous Manifestations of Immunodeficiency. Immunol Allergy Clin North Am 37:1-10 |
| Ma, Chi A; Stinson, Jeffrey R; Zhang, Yuan et al. (2017) Germline hypomorphic CARD11 mutations in severe atopic disease. Nat Genet 49:1192-1201 |
| Carlson, Ryan J; Bond, Michelle R; Hutchins, Shermaine et al. (2017) Detection of phosphoglucomutase-3 deficiency by lectin-based flow cytometry. J Allergy Clin Immunol 140:291-294.e4 |
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