GAD65 IgG autoantibodies in stiff person syndrome: clonality, avidity and persistence
Article first published online: 10 JUL 2008
© 2008 The Author(s). Journal compilation © 2008 EFNS
European Journal of Neurology
Volume 15, Issue 9, pages 973–980, September 2008
How to Cite
Skorstad, G., Hestvik, A. L., Torjesen, P., Alvik, K., Vartdal, F., Vandvik, B. and Holmøy, T. (2008), GAD65 IgG autoantibodies in stiff person syndrome: clonality, avidity and persistence. European Journal of Neurology, 15: 973–980. doi: 10.1111/j.1468-1331.2008.02221.x
- Issue published online: 11 AUG 2008
- Article first published online: 10 JUL 2008
- Received 25 January 2008 Accepted 21 May 2008
- autoimmune disease;
- cerebrospinal fluid;
- stiff person syndrome
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.