Stiff person syndrome: quantification, specificity, and intrathecal synthesis of GAD65 antibodies

Neurology. 2001 Sep 11;57(5):780-4. doi: 10.1212/wnl.57.5.780.

Abstract

Objective: To characterize the specificity of anti-GAD(65) antibodies in patients with stiff person syndrome (SPS), quantify antibody titers, and examine antibody production within the CNS.

Methods: The authors studied 18 patients with SPS and positive serum immunoreactivity to gamma-aminobutyric acid (GABA)-ergic neurons. The reactivity of serum and CSF to purified GAD antigen was examined by Western blots, and the anti-GAD(65) antibody titers in serum and CSF were quantified by ELISA and compared with 70 disease controls (49 with other autoimmune disorders and 11 with insulin-dependent diabetes mellitus). The intrathecal synthesis of anti-GAD(65) IgG was calculated, and the functional significance of the antibodies was examined by measuring the GABA levels in the CSF.

Results: The serum and CSF of all selected patients with SPS had high anti-GAD(65) titers (from 7.0 to 215 microg/mL in serum and from 92 to 2500 ng/mL in CSF) and immunoreacted strongly with recombinant GAD(65) on Western blots and with GABA-ergic neurons on rat cerebellum. Among controls, only the serum of eight patients with insulin-dependent diabetes mellitus had low anti-GAD(65) antibody titers (from 200 to 1760 ng/mL) but no reactivity to recombinant GAD(65). The CSF showed oligoclonal IgG bands in 10 (67%) of 15 patients and an increased anti-GAD(65)-specific IgG index in 11 (85%) of 13. The mean level of GABA in the CSF was lower in patients with SPS than in controls.

Conclusions: In patients with SPS, there is marked intrathecal antibody response against neuronal GAD(65) epitopes, indicating a clonal B cell activation in the CNS. Anti-GAD(65) antibodies at high titers, when confirmed with immunoblots, are highly specific for SPS and appear to impair GABA synthesis.

MeSH terms

  • Animals
  • Antibody Specificity*
  • Autoantibodies / biosynthesis*
  • Autoantibodies / blood
  • Autoantibodies / cerebrospinal fluid*
  • Cerebellum / metabolism
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / cerebrospinal fluid
  • Glutamate Decarboxylase / blood
  • Glutamate Decarboxylase / cerebrospinal fluid*
  • Glutamate Decarboxylase / immunology*
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / cerebrospinal fluid
  • Isoenzymes / blood
  • Isoenzymes / cerebrospinal fluid*
  • Isoenzymes / immunology*
  • Rats
  • Stiff-Person Syndrome / cerebrospinal fluid*
  • Stiff-Person Syndrome / immunology*

Substances

  • Autoantibodies
  • Immunoglobulin G
  • Isoenzymes
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2