Departments of Psychiatry, Yale University, New Haven, CT, USA.
Departments of Pediatrics, Stanford University School of Medicine, Stanford University, CA, USA; Immune Behavioral Health Clinic and Research Program, Stanford University School of Medicine, Stanford University, CA, USA; Division of Allergy, Immunology, Rheumatology, Stanford University School of Medicine, Stanford University, CA, USA.
Brain Behav Immun. 2024 Nov;122:241-255. doi: 10.1016/j.bbi.2024.07.044. Epub 2024 Jul 30.
Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is characterized by the abrupt onset of significant obsessive-compulsive symptoms (OCS) and/or severe food restriction, together with other neuropsychiatric manifestations. An autoimmune pathogenesis triggered by infection has been proposed for at least a subset of PANS. The older diagnosis of Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS) describes rapid onset of OCD and/or tics associated with infection with Group A Streptococcus. The pathophysiology of PANS and PANDAS remains incompletely understood. We recently found serum antibodies from children with rigorously defined PANDAS to selectively bind to cholinergic interneurons (CINs) in the striatum. Here we examine this binding in children with relapsing and remitting PANS, a more heterogeneous condition, collected in a distinct clinical context from those examined in our previous work, from children with a clinical history of Streptococcus infection. IgG from PANS cases showed elevated binding to striatal CINs in both mouse and human brain. Patient plasma collected during symptom flare decreased a molecular marker of CIN activity, phospho-riboprotein S6, in ex vivo brain slices; control plasma did not. Neither elevated antibody binding to CINs nor diminished CIN activity was seen with plasma collected from the same children during remission. These findings replicate what we have seen previously in PANDAS and support the hypothesis that at least a subset of PANS cases have a neuroimmune pathogenesis. Given the critical role of CINs in modulating basal ganglia function, these findings confirm striatal CINs as a locus of interest in the pathophysiology of both PANS and PANDAS.
儿科急性发作的神经精神综合征（PANS）的特征是突然出现明显的强迫症状（OCS）和/或严重的食物限制，同时伴有其他神经精神表现。至少一部分 PANS 患者的发病机制被认为是由感染引发的自身免疫反应。旧的儿科自身免疫性神经精神障碍伴链球菌感染（PANDAS）的诊断描述了与 A 组链球菌感染相关的 OCD 和/或抽动的快速发作。PANS 和 PANDAS 的病理生理学仍不完全清楚。我们最近发现，来自严格定义的 PANDAS 患儿的血清抗体选择性地与纹状体中的胆碱能中间神经元（CIN）结合。在这里，我们检查了在具有复发和缓解的 PANS 儿童中的这种结合，这是一种更具异质性的情况，从我们以前工作中检查的情况中收集到的，来自有链球菌感染临床病史的儿童。PANS 病例的 IgG 在小鼠和人类大脑中显示出对纹状体 CIN 的升高结合。在症状发作期间采集的患者血浆降低了 CIN 活性的分子标志物磷酸核糖蛋白 S6，而对照血浆则没有。在缓解期从同一儿童采集的血浆既没有观察到对 CIN 的抗体结合升高，也没有观察到 CIN 活性降低。这些发现复制了我们之前在 PANDAS 中看到的情况，并支持了至少一部分 PANS 病例具有神经免疫发病机制的假说。鉴于 CIN 在调节基底节功能中的关键作用，这些发现证实了纹状体 CIN 是 PANS 和 PANDAS 病理生理学的一个重要关注点。
