Frontiers in Neurology (Jan 2023)
Dual ankyrinG and subpial autoantibodies in a man with well-controlled HIV infection with steroid-responsive meningoencephalitis: A case report
- Christopher M. Bartley,
- Christopher M. Bartley,
- Thomas T. Ngo,
- Thomas T. Ngo,
- Cathryn R. Cadwell,
- Cathryn R. Cadwell,
- Cathryn R. Cadwell,
- Adil Harroud,
- Adil Harroud,
- Ryan D. Schubert,
- Ryan D. Schubert,
- Bonny D. Alvarenga,
- Bonny D. Alvarenga,
- Isobel A. Hawes,
- Isobel A. Hawes,
- Isobel A. Hawes,
- Kelsey C. Zorn,
- Trung Hunyh,
- Trung Hunyh,
- Lindsay H. Teliska,
- Andrew F. Kung,
- Shailee Shah,
- Shailee Shah,
- Jeffrey M. Gelfand,
- Jeffrey M. Gelfand,
- Felicia C. Chow,
- Felicia C. Chow,
- Matthew N. Rasband,
- Divyanshu Dubey,
- Divyanshu Dubey,
- Sean J. Pittock,
- Sean J. Pittock,
- Sean J. Pittock,
- Joseph L. DeRisi,
- Joseph L. DeRisi,
- Michael R. Wilson,
- Michael R. Wilson,
- Samuel J. Pleasure,
- Samuel J. Pleasure
Affiliations
- Christopher M. Bartley
- Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
- Christopher M. Bartley
- Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA, United States
- Thomas T. Ngo
- Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
- Thomas T. Ngo
- Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA, United States
- Cathryn R. Cadwell
- Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
- Cathryn R. Cadwell
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States
- Cathryn R. Cadwell
- Department of Pathology, University of California, San Francisco, San Francisco, CA, United States
- Adil Harroud
- Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
- Adil Harroud
- Department of Neurology, University of California, San Francisco, San Francisco, CA, United States
- Ryan D. Schubert
- Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
- Ryan D. Schubert
- Department of Neurology, University of California, San Francisco, San Francisco, CA, United States
- Bonny D. Alvarenga
- Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
- Bonny D. Alvarenga
- Department of Neurology, University of California, San Francisco, San Francisco, CA, United States
- Isobel A. Hawes
- Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
- Isobel A. Hawes
- Department of Neurology, University of California, San Francisco, San Francisco, CA, United States
- Isobel A. Hawes
- Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, United States
- Kelsey C. Zorn
- Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, United States
- Trung Hunyh
- Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
- Trung Hunyh
- Department of Neurology, University of California, San Francisco, San Francisco, CA, United States
- Lindsay H. Teliska
- Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States
- Andrew F. Kung
- School of Medicine, University of California, San Francisco, San Francisco, CA, United States
- Shailee Shah
- 0Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States
- Shailee Shah
- 1Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, United States
- Jeffrey M. Gelfand
- Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
- Jeffrey M. Gelfand
- Department of Neurology, University of California, San Francisco, San Francisco, CA, United States
- Felicia C. Chow
- Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
- Felicia C. Chow
- Department of Neurology, University of California, San Francisco, San Francisco, CA, United States
- Matthew N. Rasband
- Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States
- Divyanshu Dubey
- 2Department of Neurology, Mayo Clinic Foundation, Rochester, MN, United States
- Divyanshu Dubey
- 3Department of Laboratory Medicine and Pathology, Mayo Clinic Foundation, Rochester, MN, United States
- Sean J. Pittock
- 1Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, United States
- Sean J. Pittock
- 2Department of Neurology, Mayo Clinic Foundation, Rochester, MN, United States
- Sean J. Pittock
- 3Department of Laboratory Medicine and Pathology, Mayo Clinic Foundation, Rochester, MN, United States
- Joseph L. DeRisi
- Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, United States
- Joseph L. DeRisi
- 4Chan Zuckerberg Biohub, San Francisco, CA, United States
- Michael R. Wilson
- Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
- Michael R. Wilson
- Department of Neurology, University of California, San Francisco, San Francisco, CA, United States
- Samuel J. Pleasure
- Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
- Samuel J. Pleasure
- Department of Neurology, University of California, San Francisco, San Francisco, CA, United States
- DOI
- https://doi.org/10.3389/fneur.2022.1102484
- Journal volume & issue
-
Vol. 13
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.
Keywords
- meningoencephalitis
- axon initial segment (AIS)
- node of Ranvier
- human immunodeficiency virus (HIV)
- ankyrinG
- ANK3
