Autoimmunity in Patients With GAD-Ab and Their Relatives

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Neurological Syndromes With GAD-Ab, Organ-specific Autoimmune Diseases

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| patients with neurological syndromes and GAD-Ab<br>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?
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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 |