Prevalence of established and novel cell-surface autoantibodies in adult patients with recent onset epilepsies of unknown aetiology.
Moloney T., Adcock JE., Irani S., Kramer H., Vincent None., Lang B.
Rationale: The discovery of autoantibodies targeting the extracellular domain of neural proteins has strengthened the concept of autoimmune epilepsy. Recent studies have shown that such potentially pathogenic autoantibodies are present in approximately 10 % of patients with unselected epilepsies, particularly adult-onset focal epilepsies (Brenner at al., 2013). Some patients with these antibodies have a preferential response to immunotherapy over anti-epileptic drugs. More specifically, a clinically distinctive focal epilepsy, termed faciobrachial dystonic seizures (FBDS), is consistently associated with leucine-rich, glioma inactivated 1 (LGI1)-antibodies. FBDS are usually antiepileptic drug (AED)-refractory but immunotherapy-responsive (Irani et al., 2011). This project aims to explore the hypothesis that a significant percentage of adult patients with recent-onset focal epilepsies will harbour known and novel potentially-pathogenic neuronal autoantibodies. Methods: Sera from adults in the Oxfordshire region with a clinical diagnosis of > 1 focal seizure were tested for antibodies to known antigens including the VGKC-complex, glutamic acid decarboxylase (GAD), LGI1, contactin-associated protein 2 (CASPR2), contactin-2, N-methyl-D-aspartate receptor (NMDAR), the AMPA receptor subunits 1 and 2 and the glycine alpha 1 receptor. Patient sera found to be negative were screened on primary hippocampal cultures to test for the presence of unknown surface-reactive autoantibodies. Results: Sixty-three patients (32 male: 31 female), with a median age of 50 years (range 18-83) were recruited. Seven (11 %) patients had antibodies targeting the VGKC-complex (radioimmunoassay > 100pM). The specific targets included Lgi1 (2/7) or CASPR2 (1/7). Cell based assays revealed antibodies targeting NMDAR (1), AMPAR (1), and glycine receptor (3) in a total of 5 other patients. Additionally, a further 2 patients bound to the surface of hippocampal cultures. Conclusions: In total, 14 patients with new-onset focal epilepsies have antibodies to known and unknown antigens. Whilst judicious extrapolation of the results is warranted at this early phase of the project, the results to date indicate an autoimmune association in 22 % of adults with new-onset cryptogenic epilepsies, higher than previously reported in unselected cohorts. Further research will include clinico-serological correlations in order to identify clinical features with a high predictive value for autoimmune epilepsy.