Qualitative and quantitative evidence of anti-glutamic acid decarboxylase-specific intrathecal antibody synthesis in patients with stiff person syndrome.
BACKGROUND
The stiff person syndrome (SPS) is a CNS disorder of putative autoimmune aetiology, which is clinically characterized by severe rigidity and spasms. In most cases, SPS is associated with serum antibodies against glutamic acid decarboxylase (GAD-Ab). Recent studies suggested that GAD-Ab might be directly involved in the pathogenesis of SPS. Further support for this hypothesis would come from studies providing qualitative evidence for the presence of GAD-Ab-producing B cell clones within the CNS of patients with SPS.


OBJECTIVE
To address that issue, we (i) analysed paired cerebrospinal fluid (CSF) and serum samples from ten GAD-Ab positive patients with SPS and controls by an antigen-driven affinity blotting technique for the presence of GAD-specific oligoclonal IgG bands (OCBs) in the CSF, and (ii) examined the immunoreactive pattern of CSF and serum IgG to recombinant GAD by immunoblotting. To confirm our results quantitatively, we (iii) assessed anti-GAD antibody reactivity in CSF and serum using ELISA and evaluated the GAD-specific antibody index.


RESULTS
GAD-specific oligoclonal bands exclusively or predominately in CSF compared to the corresponding serum were detected in 10/10 patients with GAD-positive SPS but in none of the controls. Immunoblotting revealed stronger staining in the CSF, suggestive of intrathecal IgG synthesis, in 7/10 patients upon visual inspection, and in 8/10 patients upon densitometric analysis. A positive GAD-specific antibody index was found in 9/10 patients.


CONCLUSIONS
Here we demonstrate for the first time that IgG OCBs in SPS bind GAD. Our findings contribute to the ongoing discussion on whether the autoimmune process against GAD is involved in the pathogenesis of SPS by indicating that anti-GAD-Ab is produced by B cell clones within the CNS.
Jarius
S
S
Division of Clinical Neuroimmunology, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
Stich
O
O
Speck
J
J
Rasiah
Ch
Ch
Wildemann
B
B
Meinck
H M
HM
Rauer
S
S
D000328:Adult; D000368:Aged; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005968:Glutamate Decarboxylase / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D006801:Humans; D007525:Isoelectric Focusing / Q000379:methods; D008297:Male; D008875:Middle Aged; D043025:Oligoclonal Bands / Q000378:metabolism*; D016750:Stiff-Person Syndrome / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D055815:Young Adult
D043025:Oligoclonal Bands; D005968:Glutamate Decarboxylase