Glial Fibrillary Acidic Protein Autoimmunity

Abstract

Objectives:To report the clinical, biological, imaging features, and the clinical course of a French cohort of patients with glial fibrillar acidic protein (GFAP) autoantibodies.Methods:We retrospectively included all patients tested positive for GFAP antibodies in the cerebrospinal fluid, by immunohistochemistry and confirmed by cell-based assay using cells expressing human GFAPα, since 2017, from two French referral centers.Results:We identified 46 patients with GFAP antibodies. Median age at onset was 43 years, and 65% were men. Infectious prodromal symptoms were found in 82%. Other auto-immune diseases were found in 22% of patients, and coexisting neural autoantibodies in 11%. Tumors were present in 24%, and T cell dysfunction in 23%. The most frequent presentation was subacute meningoencephalitis (85%) with cerebellar dysfunction in 57% of cases. Other clinical presentation included myelitis (30%), visual (35%) and peripheral nervous system involvement (24%). MRI showed perivascular radial enhancement in 32%, periventricular T2 hyperintensity in 41%, brainstem involvement in 31%, leptomeningeal enhancement in 26%, and reversible splenial lesions in 4 cases. 33/40 patients had a monophasic course, associated to a good outcome at last follow-up (Rankin Score≤2: 89%), despite a severe clinical presentation. Adult and pediatric features are similar. Thirty-two patients were treated with immunotherapy. 11/22 patients showed negative conversion of GFAP antibodies.Interpretation:GFAP auto-immunity is mainly associated with acute/subacute meningoencephalomyelitis with prodromal symptoms, for which tumors and T cell dysfunction are frequent triggers. The majority of patients followed a monophasic course with a good outcome.

Area Postrema Syndrome in Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy

“… 3 Impairment of astrocytes might be mediated by T cells and other inflammatory components of the immune system. 3 , 4 , 29 Given that both AQP4 and GFAP are pivotal in astrocytes, we might hypothesize that impairment of astrocytes in the AP or related neural network could cause clinical symptoms of APS in autoimmune GFAP astrocytopathy. Further pathologic studies of the AP and development of animal models are needed to elucidate the pathogenesis of astrocyte dysfunction and its association with APS in GFAP-IgG–related autoimmune astrocytopathy.…”

Case Report: Semantic Variant of Primary Progressive Aphasia Associated With Anti-Glial Fibrillary Acid Protein Autoantibodies

“…The clinical spectrum of GFAP autoantibodies to date comprises patients with meningoencephalitis, headache, visual problems, often febrile temperature, abnormal movements (9), or hyponatremia (10). A recent study confirmed that the main clinical presentation associated with GFAP autoantibodies are subacute meningoencephalitis with dysfunction in cerebellar pathways (11). Myocloni and bulbar syndrome (12) as well as blindness (13) and vision loss (14) appear to be less frequent manifestations of GFAPautoantibody disease.…”

Update in autoimmune and paraneoplastic myelopathies: Newly described antigen targets and antibody testing

“…Myelitis has been demonstrated in 30% of patients ( 16 ), with one study finding myelitis as the presenting symptom in 10.5% ( 14 ). Isolated myelitis is rare and in onset study identified in 5% ( 17 ).…”

“…Patients may have a monophasic, relapsing, or progressive course despite treatment ( 14 ). Other presenting symptoms outside of myelitis may include rhomboencephalitis, cerebellar dysfunction, swallowing difficulties, cognitive difficulties , seizures, parkinsonism, myoclonus, dysautonomia, optic disc edema, optic neuritis, uveitis, and cranial nerve palsies affecting vision ( 14 , 16 ).…”

“…Coexisting autoimmunity, including AQP4, MOG, and NMDAR antibodies have been reported ( 14 , 16 ). T cell dysfunction is common, and cases of HIV, lymphopenia, exposures to anti-programmed cell death inhibitors ( 18 ), and anti-tumor necrosis factor inhibitors have been reported ( 16 ).…”