Chapter 26 - Nuclear Envelope Protein Autoantibodies/Antilamin Autoantibodies

Abstract

Over the last two decades, a number of nuclear envelope structures have been recognized as specific targets of antinuclear autoantibodies producing a rim-like staining by indirect immunofluorescence (IIF) and collectively called antinuclear envelope autoantibodies (anti-NE). This peripheral pattern results from autoreactivities directed against proteins within three components of the nuclear envelope: the nuclear lamina (lamins A, B, and C), the nuclear pore complex (glycoprotein (gp)210, p62, and translocated promoter region (Tpr)), and the inner nuclear membrane (lamina-associated polypeptide ( LAP)1, LAP2, and lamin B receptor (LBR)). Although IIF on HEp-2 cells is still the most widely used screening assay for anti-NE, accurate immunochemical tests based on enzyme-linked immunosorbent assay (ELISA) and immunoblotting with purified or recombinant antigens have been recently developed. Anti-NE are generally believed to be not pathogenic, but they can be specific markers of disease, and, therefore, clinically useful as a diagnostic tool. Immunoreactivities against components of the nuclear pore complex have been shown to be associated with primary biliary cirrhosis (PBC), whereas autoantibodies to the lamins are associated with various autoimmune diseases, such as autoimmune hepatitis, systemic lupus erythematosus, and antiphospholipid antibody syndrome. In recent years, data from different groups and countries indicated that particular PBC-specific anti-NE correlate with disease severity and may, therefore, be a marker of poor prognosis. Much less is known, however, about the clinical and prognostic role of anti-NE in other autoimmune conditions.