Neurological Syndromes With GAD-Ab Clinical Trial
Official title:
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.
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.
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