Genetic analysis: Frontal fibrosing alopecia limited to scalp with no systemic involvement

Frontal fibrosing alopecia was found to be limited to the scalp with inflammatory milieu linked to fibrosis and no systemic inflammation, suggesting possible treatment with immune-targeting therapeutics, according to a genetic analysis.

“Frontal fibrosing alopecia (FFA) is a progressive, scarring alopecia of the frontotemporal scalp that poses a substantial burden on quality of life,” Celina Dubin, BA, of the department of dermatology and Laboratory of Inflammatory Skin Diseases at the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote. “Large-scale global profiling of FFA is lacking, preventing the development of effective therapeutics.”

In the cross-sectional study, Dubin and colleagues characterized genetic components of FFA and compared those findings with normal scalp and alopecia areata using broad molecular profiling. The goal was to identify relevant biomarkers for disease severity.

The researchers enrolled 38 patients; 12 of these patients (mean age, 65.33 years; 11 women) had FFA. A total of 33,118 genes in the scalp underwent analysis using RNA sequencing. In addition, the researchers employed Olink high-throughput proteomics to identify 350 proteins in serum. The analysis also included a fibrosis gene set.

Interferon-gamma, CXCL9 and CXCL10 from the Th1 pathway were activated in FFA patient specimens but not in normal specimens.

Others that were expressed in the FFA group were genes in the T-cell activation pathway (CD2/CD3/CCL19/ICOS), the fibrosis pathway (CXCR3/FGF14/FGF22/VIM/FN1), the T-regulatory pathway (FOXP3/TGFB1/TGFB3) and the Janus kinase/JAK (JAK3/STAT1/STAT4; fold changes > 1.5; false discovery rate < 0.05 for all).

Regarding protein expression, the researchers observed only one — ADM — that was expressed in FFA serum but not in normal serum (fold changes > 1.3; false discovery rate < 0.05).

Scalp biomarkers such as IL-36RN and interleukin-25 significantly correlated with FFA severity, according to the findings. In addition, a correlation was observed between the JAK/STAT pathway and the fibrosis gene sets (correlation coefficient > 0.6; P < .05).

Limitations included the small sample size and patients being predominantly women.

“Our data characterize FFA as an inflammatory condition limited to scalp, involving Th1/JAK skewing, with associated fibrosis and elevated T-regulatory markers, suggesting the potential for disease reversibility with JAK/STAT inhibition,” the researchers wrote.