Plasma Proteome-Driven Identification of Druggable Immune Regulators of Alopecia Areata, Validated by Transcriptome and Single-Cell Mapping

Pan L, Li C, Yang L (2026)

Publication Type: Journal article

Publication year: 2026

Pages Range: 1-17

Abstract

Abstract – Introduction: Alopecia areata (AA) is an autoimmune hair-loss disorder driven by aberrant T-cell activation and immune-epithelial crosstalk. To identify actionable upstream regulators, we established a proteome-anchored multi-omics framework integrating genetic instruments, lesional transcriptomics, and single-cell immune profiling. Methods: Putative causal plasma proteins were prioritized using cis-protein quantitative trait loci-based inference across two large proteomic datasets (UKB-PPP and deCODE). Candidates were validated by differential expression in AA lesions, protein-interaction networks, and cell-type-resolved expression from scalp single-cell RNA-seq. Druggability was assessed using curated pharmacological resources, and PheWAS evaluated safety-relevant pleiotropy. Results: The pipeline identified 206 and 169 AA-associated proteins, with CD28, GZMB, and CD1C emerging as convergent immune regulators. Single-cell data showed enrichment of CD28+ effector T cells and CD1C+ myeloid subsets in lesions, linking circulating protein signals with local inflammation. Transcriptomic patterns implicated IL-2-modulated CD28 signaling and antihistamine-responsive pathways. Druggability analyses highlighted belatacept, a CD28-blocking biologic, while PheWAS indicated minimal adverse-phenotype enrichment. Conclusion: This proteome-driven framework uncovers druggable immune regulators of AA, positioning CD28 as an actionable target with a favorable safety profile and providing a generalizable strategy for autoimmune target discovery.

Authors with CRIS profile

Caihong Li Institute of Clinical and Molecular Virology

Involved external institutions

Klinikum rechts der Isar

Germany (DE)

How to cite

APA:

Pan, L., Li, C., & Yang, L. (2026). Plasma Proteome-Driven Identification of Druggable Immune Regulators of Alopecia Areata, Validated by Transcriptome and Single-Cell Mapping. , 1-17. https://doi.org/10.1159/000551293

MLA:

Pan, Lingfeng, Caihong Li, and Liehao Yang. "Plasma Proteome-Driven Identification of Druggable Immune Regulators of Alopecia Areata, Validated by Transcriptome and Single-Cell Mapping." (2026): 1-17.

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