Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy

Cecilia Zivelonghi MD MBBS (

Dr. Zivelonghi of Mayo Clinic has no relevant financial relationship to disclose.

)
Andrew McKeon MD (

Dr. Andrew McKeon of Mayo Clinic has received research funding from Alexion, Grifols, and Medimmune and has patents pending for the following IgGs as biomarkers of autoimmune neurologic disorders: septin-5, Kelch-like protein 11, GFAP, PDE10A, and MAP1B.

)
Anastasia Zekeridou MD PhD (

Dr. Zekeridou of Mayo Clinic has a patent pending on the use of PDE10A-IgG as a biomarker of paraneoplastic autoimmunity.

)
Francesc Graus MD PhD, editor. (Dr. Graus of the University of Barcelona has no relevant financial relationships to disclose.)
Originally released December 26, 2019; expires December 26, 2022

This article includes discussion of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy, autoimmune GFAP astrocytopathy, and meningoencephalitis associated with GFAP antibodies. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Autoimmune glial fibrillary acidic protein astrocytopathy is a form of monophasic or relapsing steroid-responsive meningoencephalomyelitis often accompanied by a hallmark radial periventricular brain MRI enhancement pattern and inflammatory cerebrospinal fluid with lymphocytic pleocytosis. GFAP-IgG was first described at Mayo Clinic, U.S. and subsequently confirmed by multiple international groups (Yang et al 2017).

Key points

 

• Autoimmune GFAP astrocytopathy manifests as a meningoencephalomyelitis (or limited form thereof) with dramatic steroid-responsiveness. Early relapses may occur if steroids are deescalated and discontinued quickly.

 

• Brain MRI may reveal a typical pattern of radial gadolinium enhancement; the spine MRI abnormalities are often hazy and longitudinally-extensive T2 hyperintensities with central cord enhancement.

 

CSF testing for GFAP-IgG is more specific. Both the characteristic astrocytic, filamentous immunofluorescence pattern of CNS tissue staining (meeting all criteria) and positivity for GFAP-alpha isoform-specific-IgG are required for diagnosis.

 

• In most cases the etiology is unknown; in 25% of patients a neoplasm is detected after neurologic symptoms onset (most common being ovarian teratoma).

Historical note and terminology

In 1999, Uchida and colleagues identified glial fibrillary acidic protein antibodies in the serum and cerebrospinal fluid samples of 2 pug dogs with canine necrotizing encephalitis, a severe and rapidly progressive form of encephalitis characterized by mood alteration, ataxia and seizures, and features of necrosis and lymphocytic inflammation in pathological studies (Uchida et al 1999). Further studies confirmed the presence of GFAP-IgG in larger cohorts with similar clinical phenotype (Shibuya et al 2007).

In humans, GFAP-IgG was described as a biomarker of meningoencephalomyelitis in 2016 by Fang and associates in a cohort of 16 patients who presented with subacute cognitive and behavioral impairment, inflammatory CSF, pathology consistent with lymphocytic inflammation, and robust steroid therapy-responsiveness (Fang et al 2016). Some of those cases had been previously reported, though utilizing pathologic descriptors for nomenclature, such as “nonvasculitic autoimmune inflammatory meningoencephalitis (NAIM)” (Caselli et al 1999) or “chronic microglial encephalomyelitis” (Aksamit et al 2012).

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