NEW YORK (Reuters Health)—An autoantibody to glial fibrillary acidic protein (GFAP) is associated with relapsing autoimmune meningoencephalomyelitis that is responsive to immunotherapy, researchers report.
“Autoimmune GFAP meningoencephalomyelitis is the second autoimmune neurological disease in which the target of the immune attack is recognized to be the astrocyte type of brain cell,” Dr. Vanda A. Lennon from Mayo Clinic, Rochester, Minnesota tells Reuters Health by email. “Both were first recognized in the Mayo Clinic Neuroimmunology Laboratory (in the past 12 years) and both mimic multiple sclerosis.”
After identifying this novel autoantibody for a cytosolic intermediate filament protein of astrocytes, Dr. Lennon’s team reviewed medical records to describe the features of the disorder associated with it in 16 patients with the GFAP autoantibody and a diagnosis of meningoencephalomyelitis.
IgG in all 16 patients—but in none of 173 healthy controls—intensely stained the cytoplasmic filaments in astrocyte populations. The antibody was subsequently identified in serum from 87 similar patients but not in any serum or CSF specimen from more than 100,000 patients with miscellaneous neurologic disorders.
Disabling corticosteroid-responsive meningoencephalitis or encephalitis, with or without myelitis, was the most common clinical presentation, and subacute headache was the most common symptom.
MRI identified diffuse abnormalities in periventricular white matter in nine of 12 patients and abnormal spinal findings in five of seven patients with myelopathy, according to the Sept. 12 JAMA Neurology online report.1
Most patients (13/14) had inflammatory CSF findings, five patients had oligoclonal bands, and three had elevated IgG index.
Based on all available clinical, radiologic, and CSF findings, six patients had meningoencephalitis, five had meningoencephalomyelitis, two had encephalomyelitis, two had encephalitis, and one had meningitis.
Seven patients had at least one autoimmune finding, and six had documented past or current cancer.
Eleven of 13 patients received immunotherapy, and all responded favorably to initial IV high-dose corticosteroids, although seven relapsed during dose tapering. There were no relapses among six patients who received long-term immunosuppression with mycophenolate or azathioprine.
Patient IgG binding was relatively restricted to astrocytes expressing GFAP-delta/epsilon.
“This newly recognized subacute, corticosteroid-responsive, relapsing meningoencephalomyelitis is unified by detection of a distinctive autoantibody (GFAP-specific IgG) in spinal fluid or serum,” Dr. Lennon says. “Detection of this autoantibody should prompt a search for underlying cancer (found in 1/3 of cases).”
“Testing for GFAP antibody in the patient’s spinal fluid or blood serum aids the correct diagnosis, obviates need for brain biopsy, guides the appropriate course of (immuno)therapy, and may lead to detection of an unsuspected underlying cancer (new or recurrent) that is driving the immune system to produce the antibody,” she says.
“The neurological spectrum unified by a positive test for GFAP antibody is likely broader than the tip of the iceberg we are recognizing thus far,” Dr. Lennon says.
“Tests for the antibody need to be validated rigorously to avoid false positive results,” Dr. Lennon adds. “CSF yields greater sensitivity and specificity than serum. An optimized tissue-based immunofluorescence assay is recommended for screening, with confirmation by GFAP-transfected cell-based immunofluorescence assay.”
Dr. Robert P. Lisak from Wayne State University School of Medicine, Detroit, who wrote an editorial related to this report, tells Reuters Health by email, “If a physician sees a patient with the clinical features of the encephalomyelitis described in the report by Dr. Lennon and her colleagues who has the appropriate MRI and spinal fluid findings, they should strongly suspect their patient has this immune-mediated disorder and treat with corticosteroids and/or other immunosuppressive treatments.”2
“I am looking forward to the analysis of additional patients by Dr. Lennon and her colleagues who have this antibody to the epsilon isoform of glial acidic fibrillary protein as well as to their making antibody testing for this antibody available to the neurologic community,” he says.
“We are likely to see additional disorders proven to be immune mediated and likely autoimmune etiology,” Dr. Lisak adds.
- Fang B, McKeon A, Hinson SR, et al. Autoimmune glial fibrillary acidic protein astrocytopathy: A novel meningoencephalomyelitis. JAMA Neurol. 2016 Sep 12. doi: 10.1001/jamaneurol.2016.2549. [Epub ahead of print]
- Lisak RP. Expanding the range of diagnosable autoimmune encephalopathies and encephalomyelopathies. JAMA Neurol. 2016 Sep 12. doi: 10.1001/jamaneurol.2016.2970. [Epub ahead of print]