Thymic Stromal Lymphopoietin Variation, Filaggrin Loss of Function, and the Persistence of Atopic Dermatitis

被引:66
作者
Margolis, David J. [1 ,2 ]
Kim, Brian [2 ]
Apter, Andrea J. [3 ]
Gupta, Jayanta [1 ]
Hoffstad, Ole [1 ]
Papadopoulos, Maryte [1 ]
Mitra, Nandita [1 ]
机构
[1] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA
[2] Univ Penn, Perelman Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA
[3] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA
关键词
MUTATIONS; DISEASE; EXPRESSION; CHILDREN; BARRIER; TSLP; SKIN;
D O I
10.1001/jamadermatol.2013.7954
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
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.
引用
收藏
页码:254 / 259
页数:6
相关论文
共 33 条
[1]  
Abramovits W, 2005, J AM ACAD DERMATOL, V53, pS86, DOI 10.1016/j.jaad.2005.04.034
[2]  
[Anonymous], 2004, SCIENCE
[3]   An update on the genetics of atopic dermatitis: Scratching the surface in 2009 [J].
Barnes, Kathleen C. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2010, 125 (01) :16-29
[4]   Phenotype of atopic dermatitis subjects with a history of eczema herpeticum [J].
Beck, Lisa A. ;
Boguniewicz, Mark ;
Hata, Tissa ;
Schneider, Lynda C. ;
Hanifin, Jon ;
Gallo, Rich ;
Paller, Amy S. ;
Lieff, Susi ;
Reese, Jamie ;
Zaccaro, Daniel ;
Milgrom, Henry ;
Barnes, Kathleen C. ;
Leung, Donald Y. M. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2009, 124 (02) :260-269
[5]   Adjusting for multiple testing - when and how? [J].
Bender, R ;
Lange, S .
JOURNAL OF CLINICAL EPIDEMIOLOGY, 2001, 54 (04) :343-349
[6]   Atopic dermatitis: a disease of altered skin barrier and immune dysregulation [J].
Boguniewicz, Mark ;
Leung, Donald Y. M. .
IMMUNOLOGICAL REVIEWS, 2011, 242 :233-246
[7]   Accounting for Population Stratification in Practice: A Comparison of the Main Strategies Dedicated to Genome-Wide Association Studies [J].
Bouaziz, Matthieu ;
Ambroise, Christophe ;
Guedj, Mickael .
PLOS ONE, 2011, 6 (12)
[8]   One Remarkable Molecule: Filaggrin [J].
Brown, Sara J. ;
McLean, W. H. Irwin .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2012, 132 (03) :751-762
[9]   Skin-Derived TSLP Triggers Progression from Epidermal-Barrier Defects to Asthma [J].
Demehri, Shadmehr ;
Morimoto, Mitsuru ;
Holtzman, Michael J. ;
Kopan, Raphael .
PLOS BIOLOGY, 2009, 7 (05)
[10]  
Esnault S, 2008, INT J CLIN EXP PATHO, V1, P325