Assays for Non-MS Antibodies: Principles, Techniques and Standardisation

A new field of central nervous system neuroimmunology has developed over the last 20 years. During this time new disease associated antibodies have been identified at a rate of almost one per year. Since their discovery, scientists have developed techniques to detect these antibodies in patients sera and CSF. In this lecture I will discuss these different techniques available for antibody testing and use the story of the MOG antibody assay to highlights the principles that now guide us in the development of new diagnostic tests for pathogenic antibodies. The direct comparison of different diagnostic tests and their standardisation is not easy, as we most frequently learn about their metrics from individual studies from research laboratories. I will demonstrate that we cannot compare assays from published studies unless they are performed on the same samples and the even the way we evaluate the diagnostic tests, often based on a clinical characterisation of patients, is not optimal. Finally, I will shift to the biology of autoimmunity in the context of AQP4 mediated disease and share some surprising data from our laboratory on the b-cell populations that produce AQP4 autoantibodies, which may have therapeutic implications.