학술논문
Dual ankyrinG and subpial autoantibodies in a man with well-controlled HIV infection with steroid-responsive meningoencephalitis: A case report
Document Type
article
Author
Christopher M. Bartley; Thomas T. Ngo; Cathryn R. Cadwell; Adil Harroud; Ryan D. Schubert; Bonny D. Alvarenga; Isobel A. Hawes; Kelsey C. Zorn; Trung Hunyh; Lindsay H. Teliska; Andrew F. Kung; Shailee Shah; Jeffrey M. Gelfand; Felicia C. Chow; Matthew N. Rasband; Divyanshu Dubey; Sean J. Pittock; Joseph L. DeRisi; Michael R. Wilson; Samuel J. Pleasure
Source
Frontiers in Neurology, Vol 13 (2023)
Subject
Language
English
ISSN
1664-2295
Abstract
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.