Anti-Mi2 autoantibodies target PHD fingers of SP140L and TIF1γ, while anti-TIF1γ autoantibodies primarily bind TIF1γ outside the PHD region

作者：Iago Pinal‐Fernandez, Jon Musai, María Casal-Domínguez, Katherine Pak, Mariana J. Kaplan, Blake M. Warner, Lisa G. Rider, Rohit Aggarwal, Chester V. Oddis, Siamak Moghadam‐Kia, Glòria Garrabou, Albert Selva-O’Callaghan, José C. Milisenda, John A. Chiorini, Andrew L. Mammen, Peter D. Burbelo · 发表于：Lara D. Veeken · 年份：2025 · DOI：10.1093/rheumatology/keaf426 · 被引用次数：6 · 研究领域：Inflammatory Myopathies and Dermatomyositis、Skin Diseases and Diabetes、Rheumatoid Arthritis Research and Therapies

OBJECTIVES: Plant homeodomain (PHD) fingers are present in many chromatin-binding proteins. We recently discovered that anti-Mi2 autoantibodies recognize PHD fingers in Mi2 and AIRE. The purpose of this study was to characterize anti-Mi2 autoantibody recognition of PHD fingers in SP140L and TIF1γ as well as to explore recognition of TIF1γ by both anti-TIF1γ and anti-Mi2 autoantibodies. METHODS: Luciferase immunoprecipitation system (LIPS) assays were performed to detect autoantibodies against full-length and protein fragments of SP140L and TIF1γ in serum samples from myositis patients, disease controls and healthy controls. RESULTS: Anti-Mi2 autoantibodies recognized SP140L. When a 49 amino acid fragment of the PHD finger of SP140L was used as the target, the specificity for selectively detecting anti-Mi2 autoantibodies increased. Additionally, anti-Mi2 autoantibodies weakly bound TIF1γ compared with anti-TIF1γ autoantibodies. Excluding the TIF1γ PHD finger from the TIF1γ target autoantigen eliminated cross-reactivity with anti-Mi2 autoantibodies, confirming that anti-Mi2 autoantibodies specifically target the PHD finger of TIF1γ. Switching two amino acids in the TIF1γ PHD finger to resemble those in AIRE markedly enhanced anti-Mi2 autoantibody immunoreactivity. Anti-TIF1γ autoantibodies primarily recognized the N-terminal fragment outside of the PHD finger, indicating this region contains the immunodominant epitopes. CONCLUSIONS: Anti-Mi2 autoantibodies recognize the PHD fin...