Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy: A Review of the Literature.

Fulan Shan,Youming Long,Wei Qiu

doi:10.3389/fimmu.2018.02802

Abstract

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is an autoimmune disease of the nervous system first defined in 2016. GFAP autoantibody, especially IgG that binds to GFAPα, has been reported in the cerebrospinal fluid (CSF) and serum of patients with GFAP astrocytopathy. The positive predictive value of GFAP antibody in the CSF is higher than in the serum. Tissue-based assay (TBA) and cell-based assay (CBA) are both recommended methods for the detection of GFAP antibody. GFAP astrocytopathy is accompanied by neoplasms, but the relationship between virus infection and GFAP astrocytopathy is unclear. GFAP antibody itself does not induce pathological changes; it is only a biomarker for the process of immune inflammation. The pathology of GFAP astrocytopathy in humans is heterogeneous. GFAP astrocytopathy is commonly diagnosed in individuals over 40 years old and most patients have an acute or subacute onset. Clinical manifestations include fever, headache, encephalopathy, involuntary movement, myelitis, and abnormal vision. Lesions involve the subcortical white matter, basal ganglia, hypothalamus, brainstem, cerebellum, and spinal cord. The characteristic MRI feature is brain linear perivascular radial gadolinium enhancement in the white matter perpendicular to the ventricle. Currently, there are no uniform diagnostic criteria or consensus for GFAP astrocytopathy and coexisting neural autoantibodies detected in the same patient make the diagnosis difficult. A standard treatment regimen is yet to be developed. Most GFAP astrocytopathy patients respond well to steroid therapy although some patients are prone to relapse or even die.

Highlights

The novel concept of astrocytopathy, including neuromyelitis optica spectrum disorders (NMOSD) and autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy, was recently suggested (1, 2)
Unlike NMOSD characterized by aquaporin (AQP) 4 antibody, GFAP astrocytopathy is a meningoencephalomyelitis or limited form of meningoencephalomyelitis associated with IgG binding to GFAP
The first paper to described human GFAP astrocytopathy. They describe GFAP-IgG found in serum or cerebrospinal fluid that is specific for a cytosolic intermediate filament protein of astrocytes

Summary

BACKGROUND

The novel concept of astrocytopathy, including neuromyelitis optica spectrum disorders (NMOSD) and autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy, was recently suggested (1, 2). Unlike NMOSD characterized by aquaporin (AQP) 4 antibody, GFAP astrocytopathy is a meningoencephalomyelitis or limited form of meningoencephalomyelitis associated with IgG binding to GFAP. This disease usually involves the cerebra, meninges, spinal cord and optic nerve, and manifests as fever, headache, encephalopathy, myelitis, and abnormal vision (2–13). Since 1991, reports of the clinical manifestations, images, and features of cerebrospinal fluid (CSF) in corticosteroidresponsive meningoencephalomyelitis, known as chronic or subacute corticosteroid-responsive non-vasculitic autoimmune inflammatory meningoencephalitis (NAIM), have been published (14). In 2016, a group led by Lennon (2, 3) in the Mayo Clinic published two important reports of meningoencephalitis in humans and termed the disorder autoimmune GFAP astrocytopathy. Several studies of GFAP astrocytopathy have been published to date (2–13) (Table 1)

DETECTION METHOD

No 90 Yes 13 No

Findings

FUTURE PERSPECTIVES AND CONCLUSIONS