Anti-glutamic acid decarboxylase antibodies in the serum and cerebrospinal fluid of patients with stiff-person syndrome: correlation with clinical severity.
BACKGROUND
Stiff-person syndrome (SPS) is an immune-mediated central nervous system disorder characterized by fluctuating muscle stiffness, disabling spasms, and heightened sensitivity to external stimuli. Up to 80% of patients with SPS have anti-glutamic acid decarboxylase (GAD) antibodies in the serum or cerebral spinal fluid (CSF). Whether these antibodies are clinically relevant and correlate with disease severity is unknown.


OBJECTIVE
To correlate anti-GAD antibody titers in the serum and CSF of patients with SPS with the degree of clinical severity.


METHODS
Patients studied the last 6 years.


METHODS
The Clinical Center of the National Institutes of Health, Bethesda, MD.


METHODS
Sixteen patients with typical SPS and elevated serum anti-GAD antibody titers.


METHODS
Antibody titers in serum and CSF were measured by radioimmunoassay, and the intrathecal anti-GAD-specific IgG production was calculated.


METHODS
Comparison of antibody titers with stiffness index and heightened sensitivity scores based on scales that reliably measure disease severity.


RESULTS
The mean disease duration was 11 years (range, 5-30 years). The mean anti-GAD antibody titer in the serum was 51 500 U/mL (range, 24 000-200 000 U/mL); and in the CSF, 181 U/mL (range, 30-400 U/mL). A 10-fold increased intrathecal production of GAD-specific IgG antibodies was noted. No correlation was found between antibody titers in serum or CSF with disease severity. In 4 patients, the anti-GAD antibody titers measured serially during a 2-year period did not correlate with clinical fluctuations.


CONCLUSIONS
In patients with SPS, the anti-GAD antibody titers in serum and CSF do not correlate with disease severity or duration. Anti-GAD antibodies are an excellent marker for SPS, but monitoring their titers during the course of the disease may not be of practical value.
Rakocevic
Goran
G
Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Raju
Raghavanpillai
R
Dalakas
Marinos C
MC
D000328:Adult; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood* / Q000134:cerebrospinal fluid*; D001324:Autoantigens / Q000276:immunology; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016750:Stiff-Person Syndrome / Q000201:enzymology* / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D005968:Glutamate Decarboxylase