PMID- 28951498 OWN - NLM STAT- MEDLINE DCOM- 20190708 LR - 20220318 IS - 1468-330X (Electronic) IS - 0022-3050 (Linking) VI - 89 IP - 2 DP - 2018 Feb TI - Clinical and immunological characteristics of the spectrum of GFAP autoimmunity: a case series of 22 patients. PG - 138-146 LID - 10.1136/jnnp-2017-316583 [doi] 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 GFAPalpha and GFAPdelta 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 GFAPalpha, 14/22 to both GFAPalpha and GFAPdelta and none to the GFAPdelta 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. CI - (c) Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. FAU - Iorio, Raffaele AU - Iorio R AD - Department of Neuroscience, Istituto di Neurologia, Fondazione Policlinico Universitario 'Agostino Gemelli', Universita Cattolica del Sacro Cuore, Rome, Italy. FAU - Damato, Valentina AU - Damato V AD - Department of Neuroscience, Istituto di Neurologia, Fondazione Policlinico Universitario 'Agostino Gemelli', Universita Cattolica del Sacro Cuore, Rome, Italy. FAU - Evoli, Amelia AU - Evoli A AD - Department of Neuroscience, Istituto di Neurologia, Fondazione Policlinico Universitario 'Agostino Gemelli', Universita Cattolica del Sacro Cuore, Rome, Italy. FAU - Gessi, Marco AU - Gessi M AD - Institute of Pathology, Fondazione Policlinico Universitario 'Agostino Gemelli', Universita Cattolica del Sacro Cuore, Rome, Italy. FAU - Gaudino, Simona AU - Gaudino S AD - Department of Radiological Sciences, Institute of Radiology, Fondazione Policlinico Universitario 'Agostino Gemelli', Universita Cattolica del Sacro Cuore, Rome, Italy. FAU - Di Lazzaro, Vincenzo AU - Di Lazzaro V AD - Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Universita Campus Bio.Medico di Roma, Rome, Italy. FAU - Spagni, Gregorio AU - Spagni G AD - Department of Neuroscience, Istituto di Neurologia, Fondazione Policlinico Universitario 'Agostino Gemelli', Universita Cattolica del Sacro Cuore, Rome, Italy. FAU - Sluijs, Jacqueline A AU - Sluijs JA AD - Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center, Utrecht, The Netherlands. FAU - Hol, Elly M AU - Hol EM AD - Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center, Utrecht, The Netherlands. AD - Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands. LA - eng PT - Journal Article DEP - 20170926 PL - England TA - J Neurol Neurosurg Psychiatry JT - Journal of neurology, neurosurgery, and psychiatry JID - 2985191R RN - 0 (Autoantibodies) RN - 0 (GFAP protein, human) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Glucocorticoids) RN - 0 (Immunoglobulins, Intravenous) RN - 0 (Immunologic Factors) RN - 0 (Protein Isoforms) RN - 0 (glial fibrillary astrocytic protein, mouse) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Animals MH - Autoantibodies/*immunology MH - Autoimmune Diseases of the Nervous System/complications/immunology/*physiopathology/therapy MH - Brain/diagnostic imaging MH - Breast Neoplasms/complications MH - Carcinoma/complications MH - Cerebellar Ataxia/complications/immunology/physiopathology/therapy MH - Child MH - Drug Resistant Epilepsy/complications/immunology/physiopathology/therapy MH - Encephalomyelitis/complications/immunology/physiopathology/therapy MH - Female MH - Glial Fibrillary Acidic Protein/genetics/*immunology MH - Glucocorticoids/therapeutic use MH - Humans MH - Immunoglobulins, Intravenous/therapeutic use MH - Immunologic Factors/therapeutic use MH - Immunotherapy MH - Magnetic Resonance Imaging MH - Male MH - Meningoencephalitis/complications/immunology/physiopathology/therapy MH - Mice MH - Mice, Knockout MH - Middle Aged MH - Movement Disorders/complications/immunology/physiopathology/therapy MH - Myelitis/complications/immunology/physiopathology/therapy MH - Myoclonus/complications/immunology/physiopathology/therapy MH - Optic Neuritis/complications/immunology/physiopathology/therapy MH - Ovarian Neoplasms/complications MH - Plasma Exchange MH - Protein Isoforms MH - Spinal Cord/diagnostic imaging MH - Thymoma/complications MH - Thymus Neoplasms/complications MH - Young Adult OTO - NOTNLM OT - astrocytes OT - autoantibodies OT - autoimmune encephalitis OT - autoimmune neurology OT - meningoencephalitis COIS- Competing interests: None declared. EDAT- 2017/09/28 06:00 MHDA- 2019/07/10 06:00 CRDT- 2017/09/28 06:00 PHST- 2017/06/05 00:00 [received] PHST- 2017/09/04 00:00 [revised] PHST- 2017/09/05 00:00 [accepted] PHST- 2017/09/28 06:00 [pubmed] PHST- 2019/07/10 06:00 [medline] PHST- 2017/09/28 06:00 [entrez] AID - jnnp-2017-316583 [pii] AID - 10.1136/jnnp-2017-316583 [doi] PST - ppublish SO - J Neurol Neurosurg Psychiatry. 2018 Feb;89(2):138-146. doi: 10.1136/jnnp-2017-316583. Epub 2017 Sep 26.