ADAR1 loss-of-function variants altering RNA editing define a new interferon-dependent psoriasis subtype.

Loss-of-function variants in ADAR1 cause a new interferon-dependent psoriasis subtype with early onset and strong immune signatures.

• Why it matters: Understanding genetic causes of psoriasis is crucial for developing targeted treatments, especially for subtypes driven by immune dysregulation. This work addresses the gap in knowledge about how RNA editing defects contribute to psoriasis pathogenesis.
• What they did: Researchers sequenced the genomes of families with early-onset psoriasis, identifying four rare ADAR1 mutations, and analyzed 125 additional patients, revealing a link between ADAR1 variants and increased interferon signaling through single-cell transcriptomics and functional assays.
• The result: The study demonstrates that ADAR1 loss-of-function impairs RNA editing, elevates interferon-stimulated genes, and promotes inflammation, suggesting new avenues for personalized therapy with JAK inhibitors and TYK2 inhibitors in this psoriasis subtype.