Clinical and immunological characteristics of the spectrum of GFAP autoimmunity: a case series of 22 patients

Objective To report the clinical and immunological characteristics of 22 new patients with glial fibrillar acidic protein (GFAP) autoantibodies. Methods From January 2012 to March 2017, we recruited 451 patients with suspected neurological autoimmune disease at the Catholic University of Rome. Patients' serum and cerebrospinal fluid (CSF) samples were tested for neural autoantibodies by immunohistochemistry on mouse and rat brain sections, by cell-based assays (CBA) and immunoblot. GFAP autoantibodies were detected by immunohistochemistry and their specificity confirmed by CBA using cells expressing human GFAP alpha and GFAP delta proteins, by immunoblot and immunohistochemistry on GFAP-/- mouse brain sections. Results Serum and/or CSF IgG of 22/451 (5%) patients bound to human GFAP, of which 22/22 bound to GFAP alpha, 14/22 to both GFAP alpha and GFAP delta and none to the GFAP delta isoform only. The neurological presentation was: meningoencephalomyelitis or encephalitis in 10, movement disorder (choreoathetosis or myoclonus) in 3, anti-epileptic drugs (AED)-resistant epilepsy in 3, cerebellar ataxia in 3, myelitis in 2, optic neuritis in 1 patient. Coexisting neural autoantibodies were detected in five patients. Six patients had other autoimmune diseases. Tumours were found in 3/22 patients (breast carcinoma, 1; ovarian carcinoma, 1; thymoma, 1). Nineteen patients were treated with immunotherapy and 16 patients (84%) improved. Histopathology analysis of the leptomeningeal biopsy specimen from one patient revealed a mononuclear infiltrate with macrophages and CD8+ T cells. Conclusions GFAP autoimmunity is not rare. The clinical spectrum encompasses meningoencephalitis, myelitis, movement disorders, epilepsy and cerebellar ataxia. Coexisting neurological and systemic autoimmunity are relatively common. Immunotherapy is beneficial in most cases.