Rivera-Ruiz Irene, Ungar Benjamin, Dávila-Flores Viviana, Gay-Mimbrera Jesús, Gómez-Arias Pedro J, Juan-Cencerrado Miguel, Mochón-Jiménez Carmen, Parra-Peralbo Esmeralda, Isla-Tejera Beatriz, López-Viñau López Teresa, Guttman-Yassky Emma, Ruano Juan
Inflammatory Immune-Mediated Chronic Skin Diseases Laboratory, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain.
Department of Dermatology, Reina Sofía University Hospital, Córdoba, Spain.
Front Immunol. 2025 Aug 11;16:1651019. doi: 10.3389/fimmu.2025.1651019. eCollection 2025.
Primary lymphocytic scarring alopecias (PLSAs)-including frontal fibrosing alopecia (FFA), lichen planopilaris (LPP), and central centrifugal cicatricial alopecia (CCCA)-are chronic inflammatory scalp disorders leading to irreversible follicular destruction. Despite overlapping histopathology, their molecular differences remain poorly defined. We performed the first systematic review and transcriptomic meta-analysis of human scalp biopsies in PLSAs (PROSPERO: CRD42024559969), following PRISMA 2020 guidelines. Of 1,080 records screened, eight studies met inclusion criteria; six were eligible for meta-analysis, and two were qualitatively reviewed. The batch-corrected meta-analysis identified shared and subtype-specific transcriptomic alterations. Common features included Th1/IFNγ and JAK/STAT activation, cytotoxic lymphocyte infiltration, and downregulation of epithelial keratins. FFA and LPP showed strong immune activation, while CCCA exhibited lower inflammation but increased mitochondrial stress, lipid metabolism disruption, and fibroblast-associated remodeling. Protein-protein interaction network analysis revealed convergent and divergent molecular modules spanning immune, fibrotic, metabolic, and epigenetic pathways. LPP was uniquely enriched for gene signatures linked to cardiovascular traits, suggesting novel systemic associations. Drug repurposing analyses identified candidate compounds modulating inflammation and metabolism, some reversing inflammatory signatures in brepocitinib-treated samples. This integrated molecular analysis refines our understanding of PLSA subtypes and proposes candidate biomarkers and therapeutic targets, supporting a shift toward biomarker-driven classification and personalized treatment strategies.
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024559969.
原发性淋巴细胞性瘢痕性脱发（PLSA）——包括额部纤维性脱发（FFA）、扁平苔藓样毛发角化病（LPP）和中央离心性瘢痕性脱发（CCCA）——是导致毛囊不可逆破坏的慢性炎症性头皮疾病。尽管组织病理学存在重叠，但它们的分子差异仍不清楚。我们按照PRISMA 2020指南，对PLSA患者的人类头皮活检进行了首次系统评价和转录组荟萃分析（PROSPERO：CRD42024559969）。在筛选的1080条记录中，8项研究符合纳入标准；6项符合荟萃分析条件，2项进行了定性评价。批次校正的荟萃分析确定了共同的和亚型特异性的转录组改变。共同特征包括Th1/IFNγ和JAK/STAT激活、细胞毒性淋巴细胞浸润以及上皮角蛋白下调。FFA和LPP表现出强烈的免疫激活，而CCCA炎症较低，但线粒体应激增加、脂质代谢紊乱和成纤维细胞相关重塑增加。蛋白质-蛋白质相互作用网络分析揭示了跨越免疫、纤维化、代谢和表观遗传途径的趋同和不同分子模块。LPP独特地富集了与心血管特征相关的基因特征，提示存在新的系统性关联。药物重新利用分析确定了调节炎症和代谢的候选化合物，其中一些可逆转布雷西替尼治疗样本中的炎症特征。这种综合分子分析完善了我们对PLSA亚型的理解，并提出了候选生物标志物和治疗靶点，支持向生物标志物驱动的分类和个性化治疗策略转变。
