Evolution of methods to detect paraneoplastic antibodies

An adaptive immune response in less than 1% of people who develop cancer produces antibodies against neuronal proteins. These antibodies can be associated with paraneoplastic syndromes, and their accurate detection should instigate a search for a specific cancer. Over the years, multiple systems, from indirect immunofluorescence to live cell-based assays, have been developed to identify these antibodies. As the specific antigens were identified, high throughput, multi-antigen substrates such as line blots and ELISAs were developed for clinical laboratories. However, the evolution of assays required to identify antibodies to membrane targets has shone a light on the importance of antigen conformation for antibody detection. This chapter discusses the early antibody assays used to detect antibodies to nuclear and cytosolic targets and how new approaches are required to detect antibodies to membrane targets. The chapter presents recent data that support international recommendations against the sole use of line blots for antibody detection and highlights a new antigen-specific approach that appears promising for the detection of submembrane targets.