Antigen identification in paraneoplastic and post-infectious neurological disorders.

Anti-neuronal antibodies have been conclusively shown to be pathogenic in a handful of neurological disorders but their value in diagnosis is undeniable. Nevertheless, there are instances where diseases thought have an immunological component do not have clear antibody responses associated with them This thesis aimed to identify anti-neuronal antibodies and characterise their antigens in paraneoplastic and post-infectious neurological disorders. With regard to the latter. interest in the occurrence of anti-neuronal responses in post-streptococcal neurological disorders has culminated in the identification of four candidate auto-antigens. Recombinant forms of these proteins were produced and the frequency of an antibody response in patients determined. In addition, the antigen recognised by antibodies in the serum of patients with post-infectious opsoclonus-myoclonus was characterised using protein purification techniques and the frequency of an antibody response determined. Finally, a bacteriophage expression library was employed to study a novel antibody in a patient w ith paraneoplastic disease. Our findings were unable to provide support for an antibody response against the candidate auto-antigens in post-streptococcal disease. However we were able to characterise two target antigens, one in post-streptococcal opsoclonus-myoclonus and one in paraneoplastic neurological disease. Both antigens are thought to have specific roles in the nervous system and have provided interesting opportunities for further research into there roles in neuronal, and in the case of paraneoplastic disease, tumour biology. Further investigation is required to determine the importance of the antibody response in both post-infectious and paraneoplastic disease