<p>Primary immune thrombocytopenia (ITP) is an autoimmune disorder driven by dysfunctional regulatory T cells (Tregs) that mediate platelet destruction. Here, we show that Tregs from ITP patients undergo a profound shift in subset composition and transcriptional states, with expansion of ANXA1^high and IKZF2^high populations and aberrant interferon signaling. Single-cell transcriptomic and functional analyses revealed that in normal controls, immature-like Tregs predominantly exhibit a FOXP3^high/CCR6^high phenotype, whereas in chronic ITP they adopt an ANXA1^high state enriched for interferon-stimulated gene (ISG)^high subclusters. Elevated ISG scores in chronic ITP Tregs mark a pathological transition, with RSAD2 (Viperin) emerging as a key regulator. Viperin overexpression impaired Treg suppressive function and promoted Th1-skewed activation in conventional T cells. Mechanistically, ELF1 directly binds the RSAD2 promoter and activates its transcription via increased H3K4Me3 deposition. These findings identify the ELF1-Viperin axis as the driver of Treg dysfunction in ITP and a potential target for therapeutic intervention.</p>