Janus kinase inhibition in Down syndrome: 2 cases of therapeutic benefit for alopecia areata

Individuals with Down syndrome (DS) display widespread immune dysregulation, with much increased risk of diverse autoimmune and autoinflammatory skin conditions, including alopecia areata (AA).1,2 However, the molecular basis of this autoimmune profile remains to be elucidated. Trisomy 21 (T21), the genetic cause of DS, consistently activates the interferon (IFN) response in multiple cell types, causing hypersensitivity to IFN ligands, hyperactivation of downstream Janus kinase/signal transducer activator of transcription (JAK/STAT) signaling, significant overexpression of IFN-stimulated genes,3 and changes in the circulating proteome indicative of chronic autoinflammation with many ties to increased IFN signaling.