SYSTEMATIC REVIEW article

Front. Immunol.

Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1651019

This article is part of the Research TopicNew Insights into Inflammation Driven Autoimmune Skin Disorders: Trends and ChallengesView all 3 articles

Unravelling the Transcriptomic Landscape of Primary Lymphocytic Scarring Alopecias: Systematic Review and Meta-Analysis

Provisionally accepted
Irene Rivera RuizIrene Rivera Ruiz1,2Benjamin UngarBenjamin Ungar3Viviana Dávila-FloresViviana Dávila-Flores4Jesus Gay-MimbreraJesus Gay-Mimbrera2Pedro Jesus Gomez AriasPedro Jesus Gomez Arias1,2Miguel Juan-CencerradoMiguel Juan-Cencerrado1,2Carmen Mochon JimenezCarmen Mochon Jimenez1,2Esmeralda Parra-PeralboEsmeralda Parra-Peralbo5Beatriz Isla-TejeraBeatriz Isla-Tejera2,6Teresa López-Viñau LópezTeresa López-Viñau López6*Emma Guttman-YasskyEmma Guttman-Yassky3Ruano JuanRuano Juan1*
  • 1Department of Dermatology, Hospital Universitario Reina Sofía, Córdoba, Spain
  • 2Instituto Maimonides de Investigacion Biomedica de Cordoba, Córdoba, Spain
  • 3Icahn School of Medicine at Mount Sinai, New York, United States
  • 4Department of Pathology, Hospital Universitario Reina Sofia, Córdoba, Spain
  • 5Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid SLU, Madrid, Spain
  • 6Department of Pharmacy, Hospital Universitario Reina Sofia, Córdoba, Spain

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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. Proteinprotein 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.

Keywords: scarring alopecia, Frontal fibrosing alopecia, Lichen planopilaris, central centrifugal cicatricial alopecia, Transcriptome meta-analysis, Interferon-gamma, JAK-STAT signaling, Gene Expression Profiling

Received: 20 Jun 2025; Accepted: 14 Jul 2025.

Copyright: © 2025 Rivera Ruiz, Ungar, Dávila-Flores, Gay-Mimbrera, Gomez Arias, Juan-Cencerrado, Mochon Jimenez, Parra-Peralbo, Isla-Tejera, López-Viñau López, Guttman-Yassky and Juan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Teresa López-Viñau López, Department of Pharmacy, Hospital Universitario Reina Sofia, Córdoba, Spain
Ruano Juan, Department of Dermatology, Hospital Universitario Reina Sofía, Córdoba, Spain

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Supplementary Material