Frontal Fibrosing Alopecia shows robust Th1 and JAK3 skewing.

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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, lacking effective treatments to halt disease progression.We profiled lesional and non-lesional scalp biopsies collected in 2017 from FFA patients (n=12) in comparison to scalp biopsies from alopecia areata (AA) (n=8) and control (n=8) individuals to evaluate gene and protein expression including the primary outcome (CXCL9). We determined significant differences between biomarkers by a two-sided Student's t-test adjusting p-values by FDR.Significant increases were seen in CD8+ cytotoxic T-cells, CD11c+ dendritic cells, CD103+ and CD69+ tissue-resident memory T-cells/TRM in FFA and AA versus 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 Th1/IFN (e.g. IFN-, CXCL9/CXCL10), JAK-STAT pathway (STAT1, JAK3), and fibrosis-related products (vimentin, fibronectin; p<0.05 for all), with no concomitant downregulation of hair keratins and the T-regulatory marker, FOXP3, which were decreased in AA. The stem cell markers CD200 and K15 demonstrated significantly reduced expression only in FFA (p<0.05).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.

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