Analysis of autoantibodies/antigens has very important impact for investigation of the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent progress has enabled us to detect and analyze the autoantibodies/antigens easily by using a proteomics approach. By proteomics, we can directly detect proteins as gene products as well as their alterations by post-translational modification and internal abscission which are characteristically observed in proteins. For example, we pick up autoantigens of interest as spots through combination of two-dimensional electrophoresis and western blot, and identify them by analysis using mass spectrometry. These methods allow us to use clinical specimens, including various tissues as a source of autoantigens. In this review, we introduce application of proteomics approach to autoimmune diseases, referring to our study of the autoantigens detected by anti-neuronal antibodies in SLE patients with central nervous system involvement.