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

Raffaele Iorio, Valentina Damato, Amelia Evoli, Marco Gessi, Simone Gaudino, Vincenzo Di Lazzaro, Gregorio Spagni, Jacqueline A. Sluijs, Elly M. Hol

Research output: Contribution to journalArticle

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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 GFAPÎ 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 GFAPδand none to the GFAPδisoform 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.

Original languageEnglish
Pages (from-to)138-146
Number of pages9
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume89
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

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Autoimmunity
Neuroglia
Proteins
Autoantibodies
Myelitis
Cerebellar Ataxia
Immunohistochemistry
Movement Disorders
Immunotherapy
Autoimmune Diseases
Cerebrospinal Fluid
Optic Neuritis
Myoclonus
Meningoencephalitis
Thymoma
Brain
Encephalitis
Serum
Epilepsy
Immunoglobulin G

Keywords

  • astrocytes
  • autoantibodies
  • autoimmune encephalitis
  • autoimmune neurology
  • meningoencephalitis

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

Clinical and immunological characteristics of the spectrum of GFAP autoimmunity : A case series of 22 patients. / Iorio, Raffaele; Damato, Valentina; Evoli, Amelia; Gessi, Marco; Gaudino, Simone; Di Lazzaro, Vincenzo; Spagni, Gregorio; Sluijs, Jacqueline A.; Hol, Elly M.

In: Journal of Neurology, Neurosurgery and Psychiatry, Vol. 89, No. 2, 01.02.2018, p. 138-146.

Research output: Contribution to journalArticle

Iorio, Raffaele ; Damato, Valentina ; Evoli, Amelia ; Gessi, Marco ; Gaudino, Simone ; Di Lazzaro, Vincenzo ; Spagni, Gregorio ; Sluijs, Jacqueline A. ; Hol, Elly M. / Clinical and immunological characteristics of the spectrum of GFAP autoimmunity : A case series of 22 patients. In: Journal of Neurology, Neurosurgery and Psychiatry. 2018 ; Vol. 89, No. 2. pp. 138-146.
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AU - Iorio, Raffaele

AU - Damato, Valentina

AU - Evoli, Amelia

AU - Gessi, Marco

AU - Gaudino, Simone

AU - Di Lazzaro, Vincenzo

AU - Spagni, Gregorio

AU - Sluijs, Jacqueline A.

AU - Hol, Elly M.

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N2 - 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 GFAPÎ 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 GFAPδand none to the GFAPδisoform 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.

AB - 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 GFAPÎ 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 GFAPδand none to the GFAPδisoform 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.

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KW - meningoencephalitis

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