Autoimmunity in Patients With GAD-Ab and Their Relatives

Neurological Syndromes With GAD-Ab Clinical Trial

— FamilyGAD  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04104620
• Other study ID #: FamilyGAD
• Status: Not yet recruiting
• Start date: September 30, 2019
• Est. completion date: September 30, 2020

Study information

• Verified date: September 2019
• Source: Hospices Civils de Lyon
• Contact: Jerome HONNORAT, phd
• Phone: 4 72 35 78 08
• Email: jerome.honnorat[@]chu-lyon.fr
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: September 30, 2020
• Est. primary completion date: August 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Autoimmune Diseases
• Neurological Syndromes With GAD-Ab
• Organ-specific Autoimmune Diseases
• Syndrome

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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