Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Jun;32(3):452-458.
doi: 10.1097/WCO.0000000000000676.

Autoimmune glial fibrillary acidic protein astrocytopathy

Amy Kunchok  1 , Anastasia Zekeridou  1   2 , Andrew McKeon  1   2
Affiliations
Review

Autoimmune glial fibrillary acidic protein astrocytopathy

Amy Kunchok et al. Curr Opin Neurol. 2019 Jun.

Abstract

Purpose of review: To describe a recently characterized autoimmune, inflammatory central nervous system (CNS) disorder known as autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.

Recent findings: Affected patients present with symptoms of one or more of meningitis (headache and neck ache), encephalitis (delirium, tremor, seizures, or psychiatric symptoms), and myelitis (sensory symptoms and weakness). Optic disc papillitis (blurred vision) is common. CNS inflammation is evident in characteristic T1 postgadolinium enhancement of GFAP-enriched CNS regions, and lymphocytic cerebrospinal fluid (CSF) white cell count elevation. CSF is more reliable than serum for GFAP-immunoglobulin G (IgG) testing. Ovarian teratoma commonly coexists, particularly among patients with accompanying N-methyl-D-aspartate receptor or aquaporin-4 autoimmunity. Parainfectious autoimmunity is suspected in some other patients, though the culprit organism is rarely verified. Pathophysiologic relevance of T cells is underscored by neuropathology and cases of dysregulated T-cell function (HIV or checkpoint inhibitor cancer therapy). Corticosteroid-responsiveness is a hallmark of the disease. Relapses occur in approximately 20% of patients, necessitating transition to a steroid-sparing drug. Reported outcomes vary, though in the authors' experience, early and sustained intervention usually portends recovery.

Summary: Autoimmune GFAP astrocytopathy is a treatable autoimmune CNS disease diagnosable by GFAP-IgG testing in CSF. This disease presents opportunities to explore novel mechanisms of CNS autoimmunity and inflammation.

PubMed Disclaimer

Figures

Box 1
Box 1
no caption available
FIGURE 1
FIGURE 1
Indirect immunofluorescence assay: staining pattern of glial elements within a composite of adult mouse brain and gastric tissues produced by patient GFAP-IgG in CSF. Patient IgG produces filamentous staining of: (a) brain parenchyma adjacent to the lateral ventricle (LV, 20×), most prominently in the subependymal zone (arrow); (b) pia and subpial region of cerebral cortex (Cx, 20×) and adjacent myenteric plexus glial cells (arrow heads); (c) pial and subpial midbrain, but sparing cerebellum (Cb, 20×). (d) 40× magnification of midbrain demonstrates filamentous staining around small blood vessels. CSF, cerebrospinal fluid; GFAP, glial fibrillary acidic protein; IgG, immunoglobulin G.
FIGURE 2
FIGURE 2
Characteristic T1 postgadolinium MR images of autoimmune GFAP astrocytopathy (axial brain, a–d; sagittal spine, e). Patterns of brain enhancement include: (a) radial periventricular; (b) leptomeningeal and punctate; (c) serpiginous; and (d), periependymal. Spinal cord enhancement, e, is characteristically central, often adjacent to the canal (arrow heads). GFAP, glial fibrillary acidic protein; MR, magnetic resonance.
See this image and copyright information in PMC

References

    1. Fang B, McKeon A, Hinson SR, et al. Autoimmune glial fibrillary acidic protein astrocytopathy: a novel meningoencephalomyelitis. JAMA Neurol 2016; 73:1297–1307. - PubMed

    2. The original study describing autoimmune GFAP astrocytopathy.

    1. Long Y, Liang J, Xu H, et al. Autoimmune glial fibrillary acidic protein astrocytopathy in Chinese patients: a retrospective study. Eur J Neurol 2018; 25:477–483. - PubMed

    2. This article contains a large experience and includes some pathological data.

    1. Aksamit AJ, Parisi J. Chronic microglial encephalomyelitis. Ann Neurol 2012; 72:S110.
    1. Flanagan EP, Hinson SR, Lennon VA, et al. Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: analysis of 102 patients. Ann Neurol 2017; 81:298–309. - PubMed

    2. This article is the largest and most detailed experience of autoimmune GFAP astrocytopathy published to date.

    1. Shibuya M, Matsuki N, Fujiwara K, et al. Autoantibodies against glial fibrillary acidic protein (GFAP) in cerebrospinal fluids from Pug dogs with necrotizing meningoencephalitis. J Vet Med Sci 2007; 69:241–245. - PubMed