Thymic stromal lymphopoietin variation, filaggrin loss of function, and the persistence of atopic dermatitis

JAMA Dermatol. 2014 Mar;150(3):254-9. doi: 10.1001/jamadermatol.2013.7954.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Cohort Studies
  • Confidence Intervals
  • Cytokines / genetics*
  • Dermatitis, Atopic / epidemiology
  • Dermatitis, Atopic / genetics*
  • Dermatitis, Atopic / physiopathology
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Intermediate Filament Proteins / genetics*
  • Male
  • Mutation*
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Prevalence
  • Prognosis
  • Prospective Studies
  • Recurrence
  • Registries
  • Risk Assessment
  • Severity of Illness Index

Substances

  • Cytokines
  • Intermediate Filament Proteins
  • filaggrin
  • thymic stromal lymphopoietin