Biomarkers of alopecia areata disease activity and response to corticosteroid treatment

Exp Dermatol. 2016 Apr;25(4):282-6. doi: 10.1111/exd.12918. Epub 2016 Mar 3.

Abstract

Alopecia areata (AA) is a common inflammatory disease targeting the anagen-stage hair follicle. Different cytokines have been implicated in the disease profile, but their pathogenic role is not yet fully determined. We studied biopsies of pretreatment lesional and non-lesional (NL) scalp and post-treatment (intra-lesional steroid injection) lesional scalp of 6 patchy patients with AA using immunohistochemistry and gene expression analysis. Immunohistochemistry showed increases in CD3(+) , CD8(+) T cells, CD11c(+) dendritic cells and CD1a(+) Langerhans cells within and around hair follicles of pretreatment lesional scalp, which decreased upon treatment. qRT-PCR showed in pretreatment lesional scalp (compared to NL) significant increases (P < 0.05) in expression of inflammatory markers (IL-2, IL-2RA, JAK3, IL-15), Th1 (CXCL10 and CXCL9), Th2 (IL-13, CCL17 and CCL18), IL-12/IL-23p40 and IL-32. Among these, we observed significant downregulation with treatment in IL-12/IL-23p40, CCL18 and IL-32. We also observed significant downregulation of several hair keratins in lesional scalp, with significant upregulation of KRT35, KRT75 and KRT86 in post-treatment lesional scalp. This study shows concurrent activation of Th1 and Th2 immune axes as well as IL-23 and IL-32 cytokine pathways in lesional AA scalp and defined a series of response biomarkers to corticosteroid injection. Clinical trials with selective antagonists coupled with cytokine-pathway biomarkers will be necessary to further dissect pathogenic immunity.

Keywords: alopecia areata; biomarkers; hair keratins; inflammatory cytokines.

Publication types

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

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use*
  • Alopecia Areata / metabolism*
  • Alopecia Areata / physiopathology
  • Biomarkers / metabolism*
  • Biopsy
  • Cytokines / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Hair Follicle / metabolism
  • Humans
  • Immunohistochemistry
  • Inflammation
  • Interleukins / metabolism
  • Keratins / metabolism
  • Langerhans Cells / metabolism
  • Male
  • Scalp / metabolism*
  • Th1 Cells / cytology
  • Th2 Cells / cytology

Substances

  • Adrenal Cortex Hormones
  • Biomarkers
  • Cytokines
  • IL32 protein, human
  • Interleukins
  • Keratins