Dubin Celina, Glickman Jacob W, Del Duca Ester, Chennareddy Sumanth, Han Joseph, Dahabreh Dante, Estrada Yeriel D, Zhang Ning, Kimmel Grace W, Singer Giselle, Chowdhury Mashkura, Zheng Andrew Y, Angelov Michael, Gay-Mimbrera Jesús, Ruano Ruiz Juan, Krueger James G, Pavel Ana B, Guttman-Yassky Emma
Department of Dermatology and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, New York.
Department of Dermatology and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Dermatology, University of Magna Graecia, Catanzaro, Italy.
J Am Acad Dermatol. 2022 Mar;86(3):551-562. doi: 10.1016/j.jaad.2021.05.016. Epub 2021 May 24.
Frontal fibrosing alopecia (FFA) is a progressive, scarring alopecia of the frontotemporal scalp that poses a substantial burden on quality of life. Large-scale global profiling of FFA is lacking, preventing the development of effective therapeutics.
To characterize FFA compared to normal and alopecia areata using broad molecular profiling and to identify biomarkers linked to disease severity.
This cross-sectional study assessed 33,118 genes in scalp using RNA sequencing and 350 proteins in serum using OLINK high-throughput proteomics. Disease biomarkers were also correlated with clinical severity and a fibrosis gene set.
Genes differentially expressed in lesional FFA included markers related to Th1 (IFNγ/CXCL9/CXCL10), T-cell activation (CD2/CD3/CCL19/ICOS), fibrosis (CXCR3/FGF14/FGF22/VIM/FN1), T-regulatory (FOXP3/TGFB1/TGFB3), and Janus kinase/JAK (JAK3/STAT1/STAT4) (Fold changes [FCH]>1.5, FDR<.05 for all). Only one protein, ADM, was differentially expressed in FFA serum compared to normal (FCH>1.3, FDR<.05). Significant correlations were found between scalp biomarkers (IL-36RN/IL-25) and FFA severity, as well as between JAK/STAT and fibrosis gene-sets (r>.6; P <.05).
This study was limited by a small sample size and predominantly female FFA patients.
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.
额部纤维性秃发（FFA）是一种发生于额颞部头皮的进行性瘢痕性秃发，给患者的生活质量带来了沉重负担。目前缺乏对FFA的大规模全球分析，这阻碍了有效治疗方法的开发。
通过广泛的分子分析来描述FFA与正常头皮和斑秃的差异，并确定与疾病严重程度相关的生物标志物。
这项横断面研究使用RNA测序评估头皮中的33118个基因，并使用OLINK高通量蛋白质组学评估血清中的350种蛋白质。疾病生物标志物还与临床严重程度和纤维化基因集相关联。
在FFA病变区域差异表达的基因包括与Th1（IFNγ/CXCL9/CXCL10）、T细胞活化（CD2/CD3/CCL19/ICOS）、纤维化（CXCR3/FGF14/FGF22/VIM/FN1）、调节性T细胞（FOXP3/TGFB1/TGFB3）以及Janus激酶/JAK（JAK3/STAT1/STAT4）相关的标志物（所有基因的变化倍数[FCH]>1.5，错误发现率[FDR]<0.05）。与正常血清相比，FFA血清中只有一种蛋白质（ADM）差异表达（FCH>1.3，FDR<0.05）。发现头皮生物标志物（IL-36RN/IL-25）与FFA严重程度之间存在显著相关性，JAK/STAT与纤维化基因集之间也存在显著相关性（r>.6；P<0.05）。
本研究受样本量小且主要为女性FFA患者的限制。
我们的数据表明FFA是一种局限于头皮的炎症性疾病，涉及Th1/JAK失衡，并伴有相关纤维化和调节性T细胞标志物升高，提示JAK/STAT抑制可能具有逆转疾病的潜力。
