Autoimmunity in Patients With GAD-Ab and Their Relatives

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

• Registration Number: NCT04104620
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

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.

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 Timeline

• Status Verified: 2019-09
• Study First Submitted: 2019-09-24
• Study First Submitted QC: 2019-09-24
• Study First Posted: 2019-09-26
• Last Update Submitted: 2019-09-26
• Last Update Posted: 2019-09-27
• Study Start: 2019-09-30
• Primary Completion: 2020-08-30
• Study Completion: 2020-09-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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.

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Exclusion Criteria

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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Autoimmune organ-specific diseases in patients with GAD-Ab and their relatives	12 Months	To collect the different autoimmune organ-specific diseases present in patients with GAD-Ab and their relatives

Secondary Outcome Measures

Name	Time	Method
Inheritability in neurological syndromes with GAD-Ab	12 Months	To establish potential common ways of inheritability in neurological syndromes with GAD-Ab and organ-specific autoimmune diseases