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.
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.
Funder
NIH Office of the Director
National Institute of Mental Health
National Institute of Neurological Disorders and Stroke
Howard Hughes Medical Institute
Office of the President, University of California
National Multiple Sclerosis Society
Foundation for the National Institutes of Health
Subject
Neurology (clinical),Neurology
Cited by
3 articles.
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