Detection methods for neural autoantibodies

Antibodies are part of the adaptive immune response that provides protection against microorganisms. In rare instances individuals can develop antibodies that bind to normal central nervous system structures. These antibodies have been classified into two groups depending on the subcellular location of their target antigens. Biomarker antibodies bind to cytosolic or nuclear targets. They do not impact on the normal function of the cell, but are most often paraneoplastic biomarkers that may suggest screening for different cancers. The second, more recently discovered group of antibodies recognize the three-dimensional structure of native proteins that are accessible on the cell surface. Understanding of this important difference is reflected in the nature of assays used to detect antibodies in these two groups. Western blots and, more recently, line blots, both of which use linear, denatured targets, are used to detect antibodies to intracellular targets. Newer assays have been developed that maintain the native structure of protein targets to permit detection of antibodies that recognize extracellular targets. In this chapter we describe the methods used to detect both antibody types, and discuss assay cut-offs, sample handling, and which biologic fluid to test.