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

J Neurol Neurosurg Psychiatry. 2018 Feb;89(2):138-146. doi: 10.1136/jnnp-2017-316583. Epub 2017 Sep 26.

Abstract

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 GFAPα and GFAPδ 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 GFAPα, 14/22 to both GFAPα and GFAPδ and none to the GFAPδ 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.

Keywords: astrocytes; autoantibodies; autoimmune encephalitis; autoimmune neurology; meningoencephalitis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Autoantibodies / immunology*
  • Autoimmune Diseases of the Nervous System / complications
  • Autoimmune Diseases of the Nervous System / immunology
  • Autoimmune Diseases of the Nervous System / physiopathology*
  • Autoimmune Diseases of the Nervous System / therapy
  • Brain / diagnostic imaging
  • Breast Neoplasms / complications
  • Carcinoma / complications
  • Cerebellar Ataxia / complications
  • Cerebellar Ataxia / immunology
  • Cerebellar Ataxia / physiopathology
  • Cerebellar Ataxia / therapy
  • Child
  • Drug Resistant Epilepsy / complications
  • Drug Resistant Epilepsy / immunology
  • Drug Resistant Epilepsy / physiopathology
  • Drug Resistant Epilepsy / therapy
  • Encephalomyelitis / complications
  • Encephalomyelitis / immunology
  • Encephalomyelitis / physiopathology
  • Encephalomyelitis / therapy
  • Female
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / immunology*
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use
  • Immunologic Factors / therapeutic use
  • Immunotherapy
  • Magnetic Resonance Imaging
  • Male
  • Meningoencephalitis / complications
  • Meningoencephalitis / immunology
  • Meningoencephalitis / physiopathology
  • Meningoencephalitis / therapy
  • Mice
  • Mice, Knockout
  • Middle Aged
  • Movement Disorders / complications
  • Movement Disorders / immunology
  • Movement Disorders / physiopathology
  • Movement Disorders / therapy
  • Myelitis / complications
  • Myelitis / immunology
  • Myelitis / physiopathology
  • Myelitis / therapy
  • Myoclonus / complications
  • Myoclonus / immunology
  • Myoclonus / physiopathology
  • Myoclonus / therapy
  • Optic Neuritis / complications
  • Optic Neuritis / immunology
  • Optic Neuritis / physiopathology
  • Optic Neuritis / therapy
  • Ovarian Neoplasms / complications
  • Plasma Exchange
  • Protein Isoforms
  • Spinal Cord / diagnostic imaging
  • Thymoma / complications
  • Thymus Neoplasms / complications
  • Young Adult

Substances

  • Autoantibodies
  • GFAP protein, human
  • Glial Fibrillary Acidic Protein
  • Glucocorticoids
  • Immunoglobulins, Intravenous
  • Immunologic Factors
  • Protein Isoforms
  • glial fibrillary astrocytic protein, mouse