A case of GFAP-astroglial autoimmunity presenting with reversible parkinsonism

Tomczak, Anna; Su, Elaine; Tugizova, Madina; Carlson, A. J.; Kipp, Lucas; Feng, Haojun; Han, May

doi:10.1016/j.msard.2019.101900

Cited by 17 publications

(6 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We are aware of five reports describing brain or spinal cord FDG-PET imaging in patients with GFAP-A (7-11). Three patients, including one spinal cord-imaged patient, revealed hypermetabolism (7)(8)(9). Spinal cord FDG-PET hypermetabolism has also been reported in patients with neoplastic myelopathy, neurosarcoid myelopathy, and nonsarcoid inflammatory myelopathy (12,13).…”

Section: Discussionmentioning

confidence: 75%

Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Presenting with Slowly Progressive Myelitis and Longitudinally Extensive Spinal Cord Lesions

et al. 2020

View full text Add to dashboard Cite

We report a 65-year-old man with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) who presented with gait disturbance that he had experienced for approximately half a year. On neurological examination, he displayed spastic paraplegia and autonomic dysfunctions including dysuria and constipation. Spinal cord magnetic resonance imaging showed longitudinally extensive spinal cord lesions (LESCLs) extending from the cervical to the thoracic cords. The patient was negative for anti-myelin oligodendrocyte glycoprotein and anti-aquaporin 4 antibodies. Treatment with corticosteroids and intravenous immunoglobulin resulted in a clinical improvement. It is important to distinguish GFAP-A from slowly progressive myelitis with LESCLs.

show abstract

Section: Discussionmentioning

confidence: 75%

Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Presenting with Slowly Progressive Myelitis and Longitudinally Extensive Spinal Cord Lesions

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Astrocytes, presumably the main target cell of an anti-GFAP autoimmune reaction, play a vital role in multiple processes in the brain, including synapse formation, clearance of neurotransmitters, or modulation of synaptic activity and plasticity (reviewed in Vasile et al 2017 ), and an anti-GFAP autoimmunity, as reported in our manuscript, might therefore very well be linked to several neurological disorders as well to the specific autoimmune GFAP astrocytopathy (Kunchok et al 2019 ). Moreover, recently a case of GFAP-astroglial autoimmunity presented with reversible parkinsonism (Tomczak et al 2019 ), suggesting the close relationship between these entities.…”

Section: Discussionmentioning

confidence: 97%

Plasma autoantibodies to glial fibrillary acidic protein (GFAP) react with brain areas according to Braak staging of Parkinson’s disease

et al. 2022

View full text Add to dashboard Cite

Idiopathic Parkinson’s disease (PD) is characterized by a progredient degeneration of the brain, starting at deep subcortical areas such as the dorsal motor nucleus of the glossopharyngeal and vagal nerves (DM) (stage 1), followed by the coeruleus–subcoeruleus complex; (stage 2), the substantia nigra (SN) (stage 3), the anteromedial temporal mesocortex (MC) (stage 4), high-order sensory association areas and prefrontal fields (HC) (stage 5) and finally first-order sensory association areas, premotor areas, as well as primary sensory and motor field (FC) (stage 6). Autoimmunity might play a role in PD pathogenesis. Here we analyzed whether anti-brain autoantibodies differentially recognize different human brain areas and identified autoantigens that correlate with the above-described dissemination of PD pathology in the brain. Brain tissue was obtained from deceased individuals with no history of neurological or psychiatric disease and no neuropathological abnormalities. Tissue homogenates from different brain regions (DM, SN, MC, HC, FC) were subjected to SDS-PAGE and Western blot. Blots were incubated with plasma samples from 30 PD patients and 30 control subjects and stained with anti-IgG antibodies to detect anti-brain autoantibodies. Signals were quantified. Prominent autoantigens were identified by 2D-gel-coupled mass spectrometry sequencing. Anti-brain autoantibodies are frequent and occur both in healthy controls and individuals with PD. Glial fibrillary acidic protein (GFAP) was identified as a prominent autoantigen recognized in all plasma samples. GFAP immunoreactivity was highest in DM areas and lowest in FC areas with no significant differences in anti-GFAP autoantibody titers between healthy controls and individuals with PD. The anti-GFAP autoimmunoreactivity of different brain areas correlates with the dissemination of histopathological neurodegeneration in PD. We hypothesize that GFAP autoantibodies are physiological but might be involved as a cofactor in PD pathogenesis secondary to a leakage of the blood–brain barrier.

show abstract

“…However, in GFAP autoimmunity, anti-GFAP may mediate cross-reactivity to neurons, leading to dopaminergic neuron degeneration. This would explain various clinical phenomena such as cognitive and behavioral impairments and parkinsonism, as also evidenced by the attenuation of nigrosome-1 on susceptibility-weighted images [93].…”

Section: Autoimmune Diseasesmentioning

confidence: 94%