Autoimmunity in Patients With GAD-Ab and Their Relatives (FamilyGAD)

Autoimmunity Family Background in Neurological Syndromes With Antibodies Against Glutamic-acid Decarboxylase

A group of poorly studied immune-mediated neurological syndromes are associated with antibodies against glutamic-acid decarboxylase (GAD-Ab). GAD is the rate-limiting enzyme for the synthesis of gamma aminobutyric acid (GABA) from glutamate and is expressed by inhibitory neurons of the central nervous system. Neurological syndromes with anti-GAD antibodies (GAD-Ab) are often non-paraneoplastic. They mainly include limbic encephalitis (LE), cerebellar ataxia (CA) and stiff-person syndrome (SPS). Although the pathogenic role of GAD-Ab is controversial, most patients have high serum levels and GAD-Ab are also detected in the cerebrospinal fluid (CSF) along with other inflammatory abnormalities such as oligoclonal bands. GAD-Ab may also be present in the serum of T1DM patients, as pancreatic beta cells also express GAD, but usually at much lower titers than those of neurological patients. Organ-specific autoimmune diseases, such as T1DM and autoimmune thyroid disease, are common among patients with GAD-Ab and neurological syndromes and in their relatives, suggesting a shared genetic predisposition to autoimmune disorders. This is also supported by family reports of neurological syndromes with GAD-Ab and some HLA associations described in SPS.

The aim of this study is to describe the different autoimmune organ-specific diseases present in patients with GAD-Ab and their relatives, along with to identify families with higher aggregation of autoimmune diseases and establish potential ways of inheritability.

Study Overview

• Status: Unknown
• Conditions: Neurological Syndromes With GAD-Ab; Organ-specific Autoimmune Diseases

Detailed Description

A group of poorly studied immune-mediated neurological syndromes are associated with antibodies against glutamic-acid decarboxylase (GAD-Ab). GAD is the rate-limiting enzyme for the synthesis of gamma aminobutyric acid (GABA) from glutamate and is expressed by inhibitory neurons of the central nervous system. Neurological syndromes with anti-GAD antibodies (GAD-Ab) are often non-paraneoplastic. They mainly include limbic encephalitis (LE), cerebellar ataxia (CA) and stiff-person syndrome (SPS). Although the pathogenic role of GAD-Ab is controversial, most patients have high serum levels and GAD-Ab are also detected in the cerebrospinal fluid (CSF) along with other inflammatory abnormalities such as oligoclonal bands. GAD-Ab may also be present in the serum of T1DM patients, as pancreatic beta cells also express GAD, but usually at much lower titers than those of neurological patients. Organ-specific autoimmune diseases, such as T1DM and autoimmune thyroid disease, are common among patients with GAD-Ab and neurological syndromes and in their relatives, suggesting a shared genetic predisposition to autoimmune disorders. This is also supported by family reports of neurological syndromes with GAD-Ab and some HLA associations described in SPS.

The aim of this study is to describe the different autoimmune organ-specific diseases present in patients with GAD-Ab and their relatives, along with to identify families with higher aggregation of autoimmune diseases and establish potential ways of inheritability.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with neurological syndromes and GAD-Ab included in the database from the Centre de référence des syndromes neurologiques paranéoplasiques et encéphalites auto-immunes, Lyon

Description

Inclusion Criteria:

• Patient with a well-known neurological syndrome associated with Gad-Ab (LE, CA, SPS)
• Patient with an CSF positive for GAD-Ab;
• Patient witn an Age > 18 years old.

Exclusion Criteria:

• Patient with absence of complete clinical data.
• Patient with CSF not tested or negative for GAD-Ab

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
patients with neurological syndromes and GAD-Ab; This is a non-interventional study involving clinical data already stored in the database of the Centre de référence des syndromes neurologiques paranéoplasiques et encéphalites auto-immunes, or collected by the referral physicians the day of ordinary consultations. No biological sample is necessary to perform this study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Autoimmune organ-specific diseases in patients with GAD-Ab and their relatives	To collect the different autoimmune organ-specific diseases present in patients with GAD-Ab and their relatives	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inheritability in neurological syndromes with GAD-Ab	To establish potential common ways of inheritability in neurological syndromes with GAD-Ab and organ-specific autoimmune diseases	12 Months

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Jerome HONNORAT, phd, Centre de référence des syndromes neurologiques paranéoplasiques et encéphalites auto-immunes, Lyon, France

Study record dates

Study Major Dates

• Study Start (Anticipated): September 30, 2019
• Primary Completion (Anticipated): August 30, 2020
• Study Completion (Anticipated): September 30, 2020

Study Registration Dates

• First Submitted: September 24, 2019
• First Submitted That Met QC Criteria: September 24, 2019
• First Posted (Actual): September 26, 2019

Study Record Updates

• Last Update Posted (Actual): September 27, 2019
• Last Update Submitted That Met QC Criteria: September 26, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Disease; Syndrome; Autoimmune Diseases
• Other Study ID Numbers: FamilyGAD

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