GFAP Auto-immunity : a French Cohort Study (GFAP)

Glial fibrillary acidic protein (GFAP)-Immunoglobulin G (IgG) have recently been described as a biomarker of a novel inflammatory central nervous system (CNS) disorder, termed autoimmune GFAP astrocytopathy. Thus far, four major clinical series have been published (two from Mayo Clinic USA, one from Italy and one from China). GFAP-IgG detected in serum or in cerebrospinal fluid, by tissue-based assay and confirmed by cell-based assay, are associated with encephalitis or meningoencephalitis of acute or subacute onset, less frequently with myelitis or optic disk edema. The characteristic MRI feature is brain linear perivascular radial gadolinium enhancement in the white matter perpendicular to the ventricle, consistent with the immunohistochemical staining pattern of GFAP in rodent brain sections. Approximately 20% of reported cases are associated with a neoplasm (ovarian teratoma mostly). Coexisting neural autoantibodies are described in some patients, N-methyl-D-aspartate (NMDA)-receptor (R)-IgG mostly, followed by aquaporin 4 (AQP4)-IgG. The disease is usually corticosteroid responsive although relapse can occur. In contrast, Chinese patients display poorer outcomes. Pathophysiology is not well understood but the intracellular antigen location makes GFAP-IgG unlikely pathogenic whereas animal models and neuropathologic data suggest a T-cell immune-mediated disorder.

The aim of the investigators is to report the first French cohort of patients GFAP-IgG positive. Investigators retrospectively assessed clinical, immunological and radiological features, treatment response and outcomes.

Study Overview

• Status: Unknown
• Conditions: Autoimmune GFAP Astrocytopathy
• Intervention / Treatment: Other: Description and analysis

• Study Type: Observational
• Enrollment (Anticipated): 38

Contacts and Locations

• Study Contact: Name: Géraldine PICARD; Phone Number: 04 72 35 58 42; Email: geraldine.picard@chu-lyon.fr
• Study Contact Backup: Name: Romain MARIGNIER, Dr; Phone Number: 04-72-35-75-22; Email: romain.marignier@chu-lyon.fr

Study Locations

• France
  • Bron, France, 69250
    • Recruiting
    • Hospices Civils de Lyon
    • Contact: Géraldine PICARD; Phone Number: 04 72 35 58 42; Email: geraldine.picard@chu-lyon.fr
    • Contact: Romain MARIGNIER; Phone Number: 04-72-35-75-22; Email: romain.marignier@chu-lyon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients GFAP-IgG positive in serum and/or CSF

Description

Inclusion Criteria:

• Positive GFAP-Ab in serum and/or CSF tested by immunohistochemistry on mouse brain slices and confirmed by cell-based assay (CBA) of HEK293 cells expressing GFAP.
• Diagnosis and follow-up in France
• No age limit : from 0 to unlimited age

Exclusion Criteria:

• Patients GFAP-IgG negative in serum and CSF
• Absence of complete clinicopathological data
• Foreign follow-up

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients GFAP-IgG positive in serum and/or CSF; Patients developing clinical autoimmune encephalitis or meningoencephalomyelitis with anti-GFAP antibodies, managed by the National Reference Center for Paraneoplastic Syndromes and Autoimmune Encephalitis or the National Reference Center for Centre de référence for Neuro-inflammatory diseases of the brain and the spinal cord at the Neurological Hospital of Bron.

Other: Description and analysis; Retrospective, non-interventional study, using clinical, biological, radiological and therapeutic data collected during the initial diagnosis and follow-up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Report retrospectively clinical data of patients GFAP-IgG positive.	Describe prodromes (yes or no), neurologic signs and clinical course (acute/subacute - yes or no - or progressive onset - yes or no), if admitted in intensive care units (yes or no), retrospectively provided by the treating physicians using a structured questionnaire.or progressive onset), if admitted in intensive care units, neoplastic and dysimmune associated diseases and T cell dysregulation condition .	13 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe GFAP-antibody test results.	positivity of GFAP α -IgG in cerebrospinal fluid, in serum and isoform type at diagnostic and follow up. positivity of GFAP α -IgG in cerebrospinal fluid, in serum and isoform type at diagnostic and follow up.	13 months
demographic data of patients GFAP-IgG positive : age at onset	age at onset (years) retrospectively provided by the treating physicians using a structured questionnaire	13 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
demographic data of patients GFAP-IgG positive : phenotype	Report if caucasian (yes or no) retrospectively provided by the treating physicians using a structured questionnaire	13 months
demographic data of patients GFAP-IgG positive : sex	Report if female sex (yes or no) retrospectively provided by the treating physicians using a structured questionnaire physicians using a structured questionnaire	13 months
associated conditions of patients GFAP-IgG positive	Report if neoplastic and dysimmune associated diseases and T cell dysregulation condition (yes or no) physicians using a structured questionnaire physicians using a structured questionnaire	13 months
Report cerebrospinal fluid white cell count	white cell count (/mm3)	13 months
Report cerebrospinal fluid protein level	protein level (g/L)	13 months
Report cerebrospinal fluid glucose level	glucose level (mmol/L)	13 months
Report number of oligoclonal bands in cerebrospinal fluid	number of oligoclonal bands	13 months
Describe MRI features.	Head and medullar MRI at diagnostic and follow up were reviewed by a neuroradiologist. scale) at each relapse and last follow up.	13 months
Report other paraclinic findings : electroencephalographic results.	Describe electroencephalographic results at diagnostic and follow up when done .	13 months
Report other paraclinic findings : electromyographic results.	Describe electromyographic results at diagnostic and follow up when done .	13 months
Report ophthalmic exam : visual acuity	Describe visual acuity (/10) at diagnostic and follow up when done .	13 months
Report ophthalmic exam : ocular fundus.	Describe ocular fundus at diagnostic and follow up results when done .	13 months
Report ophthalmic exam : visual field.	Describe visual field at diagnostic and follow up when done .	13 months
Report ophthalmic exam : optical coherence tomography.	Describe optical coherence tomography (RNFL thickness) at diagnostic and follow up when done .	13 months
Report histologic findings.	Describe histologic results at diagnostic and follow up when done .	13 months
Report treatments and response.	Describe acute and long-term treatments administered and response.	13 months
Report outcome.	Describe outcome (modified Rankin scale) at each relapse and last follow up.	13 months

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Study Director: Romain MARIGNIER, Centre de référence des maladies inflammatoires rares du cerveau et de la moelle, Lyon, France

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Actual): January 1, 2020
• Study Completion (Anticipated): November 1, 2020

Study Registration Dates

• First Submitted: April 17, 2020
• First Submitted That Met QC Criteria: July 3, 2020
• First Posted (Actual): July 9, 2020

Study Record Updates

• Last Update Posted (Actual): July 9, 2020
• Last Update Submitted That Met QC Criteria: July 3, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: autoimmune; Acidic Protein IgG; astrocytopathy; meningoencephalomyelitis; perivascular-radial parenchymal enhancement; paraneoplasic
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases
• Other Study ID Numbers: GFAP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No