905. The Use of Gene Immunisation To Study the Role of Antibodies to Voltage Gated Potassium Channels in Neuroimmunological Disease

Abstract

Top of pageAbstract Recently, autoantibodies have been considered to be important in some CNS diseases. There is evidence of autoantibodies being detected in sera of patients with epileptic syndromes, particularly antibodies to voltage gated potassium channels (VGKCs). VGKCs are feasible targets for autoimmune attack as they are transmembrane proteins, expressed on the cell surface, controlling repolarisation and frequency of action potentials in neurons, muscles and other excitable cells. This work involves an attempt to create an animal model of autoimmune disease using gene immunisation to induce an antibody response to a VGKC sub-unit (Kv1.2). An adenoviral vector is used to over-express the immunogen (Kv1.2) as this combines the benefit of delivering a foreign antigen and an infectious agent. Viral vectors are particularly attractive for this puirpose since they mimic natural infection and can induce potent immune responses. The hypothesis is that antibodies raised in this way could potentially cross the blood-brain barrier and cause autoimmune disease by reacting with potassium channels in brain. In preliminary studies, in which mice were inoculated sub-cutaneously with an adenoviral vector expressing GFP, elevated levels of antibodies to GFP were detected in almost all mice inoculated with AdGFP at titres of 107 and 108 pfu in 2 strains of animal. In experiments in which mice were inoculated with an adenoviral vector expressing both GFP and the Kv1.2 sub-unit (AdGFP/HBK5) elevated antibody levels to both GFP and Kv1.2 were detected in some mice. In separate experiments a viral vector expressing NF-kB inducing kinase (NIK), to induce expression of the transcription factor NF-kB (AdNIK), was inoculated together with a vector expressing the Kv1.2 sub-unit (Ad/HBK5). Again elevated levels of antibodies and to Kv1.2 could be detected. There is variation between animals but this work shows that it is possible to induce auto antibodies in mice to foreign antigens in this way.