The immune system recognizes and eliminates foreign antigens by a complex network of systems. To effectively fulfill this task the immune system has to discriminate between foreign and self antigens. The mechanisms by which this discrimination is accomplished shall not be discussed here (there are numerous excellent textbooks on immunology available). However, in autoimmune disorders this discrimination fails to a certain extent due to mechanisms currently only vaguely understood. Linked with these diseases is the occurrence of circulating autoantibodies. These are antibodies directed against self antigens of a defined nature. Autoantibodies may have a direct effect on the etiology of the disease, such as in Grave’s disease. Here, the target antigen of the autoimmune response is the acetylcholine receptor of the motoric endplate; this leads to a severe disturbance in the nervous system. In other cases, the so-called systemic autoimmune disorders, the connection between etiology and target antigen is not obvious. To what extent these auto antibodies are involved in the pathogenesis of the corresponding disease is not exactly known. In the systemic diseases the target antigen commonly resides within the cell, especially within the cell nucleus. Table 7.1. Features of some of the most important nuclear autoantigensa Antigen Molecular identity Disease Indirect cytoimmunofluorescence Western blot SM RNP Scl-70 CENP Fibrillarin PM/Scl Ro (SSA) La (SSB) AMA Core proteins of snRNP’s U1-snRNP Topoisomerase I Centromere-associated proteins CENP-A, B, C Protein component of U3-snoRNP Nucleolar particle of unknown function Protein component of hY-RNP RNA-polymerase III associated factor Subunits of mitochondrial 2-oxo-acid dehydrogenase complex SLE SLE overlap Scleroderma Scleroderma Scleroderma Polymyositis scleroderma overlap Sjogren’s syndrome Sjogren’s syndrome PBC Speckled nuclear staining no staining of nucleoli Similar to Sm, occasionally more granular Fine speckled nuclear staining, frequent staining of the nucleolus Centromere staining Clumpy, nucleolar staining Homogeneous, nucleolar staining Fine, granular nuclear staining Fine, granular nuclear staining Large, granular cytoplasmic staining frequently accompanied by multiple nuclear speckles (sp100 antigen) B-protein (26–20 kDa) 70 kDa 30 kDa proteins 100 kDa protein (degradation product of 70 kDa) CENP-A (19.5 kDa) CENP-B (80 kDa) 36 kDa protein 100 kDa, 75 kDa proteins some smaller proteins 60 kDa, 52 kDa proteins 48 kDa protein 70–74 kDa protein frequently 100 kDa (sp100 antigen)