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

This study on alopecia areata (AA) utilized a proteome-anchored multi-omics framework to identify druggable immune regulators. By analyzing two large proteomic datasets and validating findings through transcriptomics and single-cell RNA sequencing, researchers identified 206 and 169 AA-associated proteins, with CD28, GZMB, and CD1C as key immune regulators. The study highlighted the role of CD28⁺ effector T cells and CD1C⁺ myeloid subsets in AA lesions, suggesting IL-2–modulated CD28 signaling as a potential therapeutic target. Druggability analysis identified belatacept, a CD28-blocking biologic, as a promising treatment with minimal adverse effects, offering a new strategy for autoimmune target discovery.