Clinical trial NCT04104620: Autoimmunity in Patients With GAD-Ab and Their Relatives
Official title: Autoimmunity Family Background in Neurological Syndromes With Antibodies Against Glutamic-acid Decarboxylase
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Neurological Syndromes With GAD-Ab
Organ-specific Autoimmune Diseases
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2019-09-26
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Autoimmune organ-specific diseases in patients with GAD-Ab and their relatives
timeFrame: 12 Months
Secondary outcomes:
measure: Inheritability in neurological syndromes with GAD-Ab
timeFrame: 12 Months
Other outcomes:
Locations:
Study officials:
affiliation: Centre de référence des syndromes neurologiques paranéoplasiques et encéphalites auto-immunes, Lyon, France
name: Jerome HONNORAT, phd
role: PRINCIPAL_INVESTIGATOR
References: