Han Velda X, Nishida Hiroya, Keating Brooke A, Gloss Brian S, Lau Xianzhong, Dissanayake Ruwani, Hayes Jessica, Mohammad Shekeeb S, Patel Shrujna, Dale Russell C
Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, NSW, Australia.
Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore.
Neurol Neuroimmunol Neuroinflamm. 2025 Nov;12(6):e200467. doi: 10.1212/NXI.0000000000200467. Epub 2025 Sep 15.
Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by infection-provoked abrupt-onset obsessive compulsive disorder (OCD) and neurodevelopmental regression. Owing to the neuroimmune hypothesis, we investigated the effects of IV immunoglobulin (IVIg) on cell-specific gene expression.
Single-cell RNA sequencing of peripheral immune cells was performed in 5 children with PANS (median age 8 (5.5-16) years), before and after administering open-label IVIg, compared with 4 controls (median age 13.5 [IQR 12-15] years).
The index PANS event (age 1.8-13 years) involved abrupt eating restriction (n = 5), developmental regression (n = 4), and OCD (n = 3). A total of 144,470 cells were sequenced and clustered into 11 cell types. Children with PANS before IVIg compared with controls showed downregulated immune pathways (defense response, innate immunity, secretory granules) in most cell types, with natural killer (NK) cells showing upregulated immune pathways (response to corticosteroid), supporting baseline "immune dysregulation." Ribosomal pathways were upregulated in neutrophils and CD8 T cells but downregulated in NK cells. In children with PANS after IVIg, the baseline immune and ribosomal pathway abnormalities were reversed and histone modification pathways (histone methyltransferase, chromatin) were downregulated in neutrophils and NK cells.
We propose that PANS is an epigenetic immune brain disorder with cellular epigenetic, ribosomal, and immune dysregulation. Epigenetic and immune-modulating therapies, such as IVIg, may have disease-modifying effects.
儿童急性起病神经精神综合征（PANS）的特征是感染诱发的急性起病强迫症（OCD）和神经发育倒退。基于神经免疫假说，我们研究了静脉注射免疫球蛋白（IVIg）对细胞特异性基因表达的影响。
对5例PANS患儿（中位年龄8（5.5 - 16）岁）在开放标签静脉注射免疫球蛋白前后进行外周免疫细胞单细胞RNA测序，并与4例对照（中位年龄13.5[四分位间距12 - 15]岁）进行比较。
PANS索引事件（年龄1.8 - 13岁）包括突然饮食限制（n = 5）、发育倒退（n = 4）和强迫症（n = 3）。共对144,470个细胞进行了测序并聚类为11种细胞类型。与对照组相比，静脉注射免疫球蛋白前的PANS患儿在大多数细胞类型中免疫途径（防御反应、固有免疫、分泌颗粒）下调，而自然杀伤（NK）细胞的免疫途径（对皮质类固醇的反应）上调，支持基线“免疫失调”。核糖体途径在中性粒细胞和CD8 T细胞中上调，但在NK细胞中下调。在静脉注射免疫球蛋白后的PANS患儿中，基线免疫和核糖体途径异常得到逆转，中性粒细胞和NK细胞中的组蛋白修饰途径（组蛋白甲基转移酶、染色质）下调。
我们提出PANS是一种具有细胞表观遗传、核糖体和免疫失调的表观遗传免疫脑疾病。表观遗传和免疫调节疗法，如静脉注射免疫球蛋白，可能具有改善疾病的作用。
