AUTHOR=Bartley Christopher M. , Ngo Thomas T. , Cadwell Cathryn R. , Harroud Adil , Schubert Ryan D. , Alvarenga Bonny D. , Hawes Isobel A. , Zorn Kelsey C. , Hunyh Trung , Teliska Lindsay H. , Kung Andrew F. , Shah Shailee , Gelfand Jeffrey M. , Chow Felicia C. , Rasband Matthew N. , Dubey Divyanshu , Pittock Sean J. , DeRisi Joseph L. , Wilson Michael R. , Pleasure Samuel J. TITLE=Dual ankyrinG and subpial autoantibodies in a man with well-controlled HIV infection with steroid-responsive meningoencephalitis: A case report JOURNAL=Frontiers in Neurology VOLUME=13 YEAR=2023 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.1102484 DOI=10.3389/fneur.2022.1102484 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.