Dual ankyrinG and subpial autoantibodies in a man with well-controlled HIV infection with steroid-responsive meningoencephalitis: A case report.

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.
Competing Interests: CB owns shares in NowRx Inc. JG has received unrelated clinical trial support through UCSF from Roche/Genentech and Vigil Neurosciences, personal fees for consulting from Biogen, and personal fees for medical-legal consulting. FC has received personal fees for medical-legal consulting. SS has received personal compensation for serving on medical advisory boards for Alexion Pharmaceuticals, and Horizon Therapeutics. DD has patents pending for KLHL11-IgG, LUZP4-IgG, and cavin-4-IgG as markers of neurological autoimmunity. DD has also received funding from the US Department of Defense (DOD) (CA210208). DD has consulted for UCB, Immunovant, Argenx, and Astellas. All compensation for consulting activities is paid directly to Mayo Clinic. SeP has received personal compensation for serving as a consultant for Genentech, Sage Therapeutics, and Astellas. He's received personal compensation for serving on scientific advisory boards or data safety monitoring boards for F. Hoffman-LaRoche AG, Genentech, and UCB. His institution has received compensation for serving as a consultant for Astellas, Alexion, and Viela Bio/MedImmune. All compensation is paid to Mayo Clinic. He has received research support from Alexion, Viela Bio/MedImmune, Roche/Genentech. He has a patent, Patent# 8,889,102 (Application#12-678350, Neuromyelitis Optica Autoantibodies as a Marker for Neoplasia)—issued; a patent, Patent# 9,891,219B2 (Application#12-573942, Methods for Treating Neuromyelitis Optica (NMO) by Administration of Eculizumab to an individual that is Aquaporin-4 (AQP4)-IgG Autoantibody positive)—issued. JD has received grants from the Chan Zuckerberg Biohub, personal fees from the Public Health Company and from Allen & Company. MW has received unrelated grants from Roche/Genentech and Novartis as well as speaking honoraria from Novartis, Takeda, WebMD and Genentech. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Bartley, Ngo, Cadwell, Harroud, Schubert, Alvarenga, Hawes, Zorn, Hunyh, Teliska, Kung, Shah, Gelfand, Chow, Rasband, Dubey, Pittock, DeRisi, Wilson and Pleasure.)