GAD65 IgG autoantibodies in stiff person syndrome: clonality, avidity and persistence

Eur J Neurol. 2008 Sep;15(9):973-80. doi: 10.1111/j.1468-1331.2008.02221.x. Epub 2008 Jul 10.


Background and purpose: Persistent intrathecal production of IgG autoantibodies against glutamic acid decarboxylase 65 (GAD65 IgG) and oligoclonal IgG of undetermined specificity has been reported in stiff person syndrome (SPS).

Methods: To chart the avidity and clonal patterns of GAD65 IgG, we performed scatchard plot of binding characteristics and isoelectric focusing-immunoblot of cerebrospinal fluid (CSF) and serum from five SPS patients.

Results: Oligoclonal GAD65 IgG bands, predominantly restricted to the IgG1 subclass, were detected in CSF and serum in all patients. The distribution of GAD65-specific IgG bands in serum and CSF revealed intrathecal synthesis of oligoclonal GAD65 IgG in all five patients, whilst radioimmunoassay demonstrated intrathecal synthesis of GAD65 IgG in four. The binding avidity of GAD65 IgG from CSF was more than 10 times higher than in serum in two of the patients but did not differ substantially in the remaining three. These differences were not related to symptom severity. The pattern of oligoclonal GAD65 IgG bands in CSF and serum in three patients examined remained unchanged for up to 7 years after symptom debut.

Conclusion: This study confirms the persistent systemic and intrathecal production of GAD65-specific IgG in SPS, and further shows that this immune response is oligoclonal and mediated by a stable population of affinity maturated B cell clones.

MeSH terms

  • Adult
  • Aged
  • Antibody Affinity
  • Autoantibodies / blood
  • Autoantibodies / cerebrospinal fluid
  • Autoantibodies / immunology*
  • Autoantigens / immunology*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Clone Cells / immunology
  • Clone Cells / pathology
  • Female
  • Glutamate Decarboxylase / immunology*
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / cerebrospinal fluid
  • Immunoglobulin G / immunology*
  • Isoelectric Focusing
  • Male
  • Middle Aged
  • Nervous System Diseases / blood
  • Nervous System Diseases / cerebrospinal fluid
  • Nervous System Diseases / immunology
  • Oligoclonal Bands / cerebrospinal fluid
  • Stiff-Person Syndrome / blood
  • Stiff-Person Syndrome / cerebrospinal fluid
  • Stiff-Person Syndrome / complications
  • Stiff-Person Syndrome / immunology*
  • Thyroiditis, Autoimmune / blood
  • Thyroiditis, Autoimmune / cerebrospinal fluid
  • Thyroiditis, Autoimmune / complications
  • Thyroiditis, Autoimmune / immunology


  • Autoantibodies
  • Autoantigens
  • Immunoglobulin G
  • Oligoclonal Bands
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2