Premium
Frontal fibrosing alopecia shows robust T helper 1 and Janus kinase 3 skewing
Author(s) -
Del Duca E.,
Ruano Ruiz J.,
Pavel A.B.,
Sanyal R.D.,
Song T.,
GayMimbrera J.,
Zhang N.,
Estrada Y.D.,
Peng X.,
RenertYuval Y.,
Phelps R.G.,
Paus R.,
Krueger J.G.,
GuttmanYassky E.
Publication year - 2020
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.19040
Subject(s) - alopecia areata , downregulation and upregulation , hair follicle , cd8 , medicine , fibrosis , immunology , biology , endocrinology , immune system , pathology , biochemistry , gene
Summary Background Frontal fibrosing alopecia (FFA) is a scarring alopecia with unclear pathogenesis and a progressive course. The disease has a major impact on patients’ quality of life and there is a lack of effective treatment to halt disease progression. Methods We profiled lesional and nonlesional scalp biopsies collected in 2017 from patients with FFA ( n = 12) compared with scalp biopsies from patients with alopecia areata (AA) ( n = 8) and controls ( n = 8) to evaluate gene and protein expression, including the primary outcome (CXCL9). We determined significant differences between biomarkers using a two‐sided Student's t ‐test adjusting P ‐values by false discovery rate. Results Significant increases were seen in CD8+ cytotoxic T cells, CD11c+ dendritic cells, CD103+ and CD69+ tissue‐resident memory T cells in FFA and AA vs. control scalp ( P < 0·05), with corresponding significantly upregulated granzyme B mRNA, particularly in FFA ( P < 0·01). In AA, cellular infiltrates were primarily concentrated at the bulb, while in FFA these were mainly localized at the bulge. FFA demonstrated significant upregulation of T helper 1/intereferon (IFN) (IFN‐γ, CXCL9/CXCL10), the Janus kinase/signal transducers and activators of transcription (JAK‐STAT) pathway (STAT1, JAK3) and fibrosis‐related products (vimentin, fibronectin; P < 0·05), with no concomitant downregulation of hair keratins and the T‐regulatory marker, forkhead box P3, which were decreased in AA. The stem cell markers CD200 and K15 demonstrated significantly reduced expression only in FFA ( P < 0·05). Conclusions These data suggest that follicular damage and loss of stem cells in FFA may be mediated through immune attack in the bulge region, with secondary fibrosis and reduced but still detectable stem cells. JAK/STAT‐targeting treatments may be able to prevent permanent follicular destruction and fibrosis in early disease stages.