David J Margolis1, Brian Kim2, Andrea J Apter3, Jayanta Gupta4, Ole Hoffstad4, Maryte Papadopoulos4, Nandita Mitra4. 1. Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia 2Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia. 2. Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia. 3. Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia. 4. Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Abstract
IMPORTANCE: Atopic dermatitis (AD) is a common chronic illness of childhood. OBJECTIVE: To evaluate the association between thymic stromal lymphopoietin (TSLP) variation and the persistence of skin symptoms of AD. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study was conducted in the general community. Participants included 796 children enrolled in the Pediatric Eczema Elective Registry. EXPOSURE Evaluation of TSLP variation. MAIN OUTCOMES AND MEASURES: Self-reported outcome of whether a child's skin had no symptoms of AD and required no medications for 6 months at 6-month intervals. RESULTS: We evaluated 14 variants of TSLP. The variant rs1898671 was significantly associated with the outcome in white children (P = .01). As measured by overlapping CIs, similar odds ratios (ORs) were noted among whites (OR, 1.72; 95% CI, 1.11-2.66) and African Americans (1.33; 0.52-3.45). Further within the subcohort of individuals with a filaggrin protein (FLG) loss-of-function mutation, those with TSLP variation were more likely to have less-persistent disease (OR, 4.92; 95% CI, 2.04-11.86). CONCLUSIONS AND RELEVANCE: The TSLP variation is associated with less persistent AD. Therefore, TSLP may be a potential therapeutic target for the treatment of AD, especially in individuals with diminished barrier function due to FLG mutations. This is an attractive hypothesis that can be tested in clinical trials.
IMPORTANCE: Atopic dermatitis (AD) is a common chronic illness of childhood. OBJECTIVE: To evaluate the association between thymic stromal lymphopoietin (TSLP) variation and the persistence of skin symptoms of AD. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study was conducted in the general community. Participants included 796 children enrolled in the Pediatric Eczema Elective Registry. EXPOSURE Evaluation of TSLP variation. MAIN OUTCOMES AND MEASURES: Self-reported outcome of whether a child's skin had no symptoms of AD and required no medications for 6 months at 6-month intervals. RESULTS: We evaluated 14 variants of TSLP. The variant rs1898671 was significantly associated with the outcome in white children (P = .01). As measured by overlapping CIs, similar odds ratios (ORs) were noted among whites (OR, 1.72; 95% CI, 1.11-2.66) and African Americans (1.33; 0.52-3.45). Further within the subcohort of individuals with a filaggrin protein (FLG) loss-of-function mutation, those with TSLP variation were more likely to have less-persistent disease (OR, 4.92; 95% CI, 2.04-11.86). CONCLUSIONS AND RELEVANCE: The TSLP variation is associated with less persistent AD. Therefore, TSLP may be a potential therapeutic target for the treatment of AD, especially in individuals with diminished barrier function due to FLG mutations. This is an attractive hypothesis that can be tested in clinical trials.
Authors: Lisa A Beck; Mark Boguniewicz; Tissa Hata; Lynda C Schneider; Jon Hanifin; Rich Gallo; Amy S Paller; Susi Lieff; Jamie Reese; Daniel Zaccaro; Henry Milgrom; Kathleen C Barnes; Donald Y M Leung Journal: J Allergy Clin Immunol Date: 2009-06-27 Impact factor: 10.793
Authors: Klara Stefflova; Matthew C Dulik; Jill S Barnholtz-Sloan; Athma A Pai; Amy H Walker; Timothy R Rebbeck Journal: PLoS One Date: 2011-01-06 Impact factor: 3.240
Authors: Padraic G Fallon; Takashi Sasaki; Aileen Sandilands; Linda E Campbell; Sean P Saunders; Niamh E Mangan; John J Callanan; Hiroshi Kawasaki; Aiko Shiohama; Akiharu Kubo; John P Sundberg; Richard B Presland; Philip Fleckman; Nobuyoshi Shimizu; Jun Kudoh; Alan D Irvine; Masayuki Amagai; W H Irwin McLean Journal: Nat Genet Date: 2009-04-06 Impact factor: 38.330
Authors: Frances J D Smith; Alan D Irvine; Ana Terron-Kwiatkowski; Aileen Sandilands; Linda E Campbell; Yiwei Zhao; Haihui Liao; Alan T Evans; David R Goudie; Sue Lewis-Jones; Gehan Arseculeratne; Colin S Munro; Ann Sergeant; Gráinne O'Regan; Sherri J Bale; John G Compton; John J DiGiovanna; Richard B Presland; Philip Fleckman; W H Irwin McLean Journal: Nat Genet Date: 2006-01-29 Impact factor: 38.330
Authors: Brian S Kim; Kelvin Wang; Mark C Siracusa; Steven A Saenz; Jonathan R Brestoff; Laurel A Monticelli; Mario Noti; Elia D Tait Wojno; Thomas C Fung; Masato Kubo; David Artis Journal: J Immunol Date: 2014-08-25 Impact factor: 5.422
Authors: Sunna Thorsteinsdottir; Jakob Stokholm; Jacob P Thyssen; Sarah Nørgaard; Jonathan Thorsen; Bo L Chawes; Klaus Bønnelykke; Johannes Waage; Hans Bisgaard Journal: JAMA Dermatol Date: 2019-01-01 Impact factor: 10.282
Authors: Carolyn Lou; Nandita Mitra; Bradley Wubbenhorst; Kurt D'Andrea; Ole Hoffstad; Brian S Kim; Albert Yan; Andrea L Zaenglein; Zelma Chiesa Fuxench; Katherine L Nathanson; David J Margolis Journal: Ann Allergy Asthma Immunol Date: 2019-09-04 Impact factor: 6.347