Arguments for and against pathogenic role of anti-GAD antibodies in SPS
| For | Against |
|---|---|
| SPS is characterised by increased muscle activity secondary to decreased inhibition of the CNS. GABA is the main inhibitory neurotransmitter in the CNS and is produced by GAD | GAD is an intracellular enzyme and is not readily accessible to antibodies |
| Decreased levels of GABA have been demonstrated in the CSF and brain parenchyma of patients with SPS | Spontaneous internalisation of anti-GAD antibodies into neurons has not been demonstrated |
| Patients with SPS frequently have high blood and CSF levels of anti-GAD antibodies | Some patients with SPS with SPS do not have anti-GAD antibodies |
| Experiments in tissues or cell cultures have demonstrated that anti-GAD antibodies from patients with SPS co-localise with neuronal GAD and inhibit this enzyme | Other antibodies (ie, anti-GlyR) and cellular immune response may play a role in the pathogenesis. There is no correlation between titres of anti-GlyR antibodies and anti-GAD antibodies |
| Some features of SPS have been transferred to mice using the serum of affected patients | Anti-GAD antibodies have been observed in other conditions besides SPS |
| Anti-GAD antibodies in patients with SPS are directed to several epitopes of GAD and it has been speculated that some of them may be pathogenic | Blood and CSF levels of anti-GAD antibodies do not necessarily correlate with clinical fluctuations or severity |
| GABA enhancing medications are helpful for most patients with SPS | Clinical improvement is not always related to lowering the titre of anti-GAD antibodies |
anti-GlyR, glycine-α1 receptor antibodies; CNS, central nervous system; CSF, cerebrospinal fluid; GABA, γ-aminobutyric acid; GAD, glutamic acid decarboxylase; SPS, Stiff-person syndrome.