神经侵袭性感染是人类免疫缺陷病毒(HIV)感染者脑膜脑炎的最常见原因。但已经报道了自身免疫性病因。我们介绍了一名患有HIV感染的51岁男子,患有类固醇反应性脑膜脑炎,其综合病原体检测无法诊断。随后的基于组织的急性期脑脊液免疫荧光显示抗神经抗体定位于轴突初始段(AIS),Ranvier(NoR)的节点,和下空间。噬菌体展示免疫沉淀测序将ankyrinG(AnkG)鉴定为主要的候选自身抗原。编码PhIP-Seq鉴定的AnkG表位中和的CSFIgG与AIS和NoR结合的合成阻断肽,从而证实了单表位AnkG抗体应答。然而,下免疫染色持续存在,表明存在额外的自身抗体。对档案组织染色的审查在患有转移性卵巢癌和癫痫发作的60岁女性中鉴定了候选AnkG自身抗体,随后通过基于细胞的测定进行了验证。通过基于组织的测定和/或对照CSF中的PhIP-Seq未检测到AnkG抗体(N=39),HIVCSF(N=79),或其他疑似和确诊的神经炎性CSF病例(N=1,236)。因此,CSF中的AnkG自身抗体很少见,但扩展了与神经系统自身免疫相关的AIS和NoR自身抗体的目录。
Neuroinvasive infection is the most common cause of meningoencephalitis in people living with human immunodeficiency virus (HIV), but autoimmune etiologies have been reported. We present the
case of a 51-year-old man living with HIV infection with steroid-responsive meningoencephalitis whose comprehensive pathogen testing was non-diagnostic. Subsequent tissue-based immunofluorescence with acute-phase cerebrospinal fluid revealed anti-neural antibodies localizing to the axon initial segment (AIS), the node of Ranvier (NoR), and the subpial space. Phage display immunoprecipitation sequencing identified ankyrinG (AnkG) as the leading candidate autoantigen. A synthetic blocking peptide encoding the PhIP-Seq-identified AnkG epitope neutralized CSF IgG binding to the AIS and NoR, thereby confirming a monoepitopic AnkG antibody response. However, subpial immunostaining persisted, indicating the presence of additional autoantibodies. Review of archival tissue-based staining identified candidate AnkG autoantibodies in a 60-year-old woman with metastatic ovarian cancer and seizures that were subsequently validated by cell-based assay. AnkG antibodies were not detected by tissue-based assay and/or PhIP-Seq in control CSF (N = 39), HIV CSF (N = 79), or other suspected and confirmed neuroinflammatory CSF cases (N = 1,236). Therefore, AnkG autoantibodies in CSF are rare but extend the catalog of AIS and NoR autoantibodies associated with neurological autoimmunity.