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

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

doi:10.3389/fneur.2022.1102484

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

Front Neurol. 2023 Jan 23:13:1102484. doi: 10.3389/fneur.2022.1102484. eCollection 2022.

Authors

Christopher M Bartley^{1

2}, Thomas T Ngo^{1

2}, Cathryn R Cadwell^{1

3

4}, Adil Harroud^{1

5}, Ryan D Schubert^{1

5}, Bonny D Alvarenga^{1

5}, Isobel A Hawes^{1

5

6}, Kelsey C Zorn⁷, Trung Hunyh^{1

5}, Lindsay H Teliska⁸, Andrew F Kung⁹, Shailee Shah^{10

11}, Jeffrey M Gelfand^{1

5}, Felicia C Chow^{1

5}, Matthew N Rasband⁸, Divyanshu Dubey^{12

13}, Sean J Pittock^{11

12

13}, Joseph L DeRisi^{7

14}, Michael R Wilson^{1

5}, Samuel J Pleasure^{1

5}

Affiliations

¹ Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States.
² Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA, United States.
³ Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States.
⁴ Department of Pathology, University of California, San Francisco, San Francisco, CA, United States.
⁵ Department of Neurology, University of California, San Francisco, San Francisco, CA, United States.
⁶ Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, United States.
⁷ Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, United States.
⁸ Department of Neuroscience, Baylor College of Medicine, Houston, TX, United States.
⁹ School of Medicine, University of California, San Francisco, San Francisco, CA, United States.
¹⁰ Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States.
¹¹ Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, United States.
¹² Department of Neurology, Mayo Clinic Foundation, Rochester, MN, United States.
¹³ Department of Laboratory Medicine and Pathology, Mayo Clinic Foundation, Rochester, MN, United States.
¹⁴ Chan Zuckerberg Biohub, San Francisco, CA, United States.

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: ANK3; ankyrinG; autoantibody; autoimmune; axon initial segment (AIS); human immunodeficiency virus (HIV); meningoencephalitis; node of Ranvier.

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Case Reports

Abstract

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