Molecular characterization of the Ro/SS-A autoimmune response

Human Ro/SS-A (Ro) antibodies (anti-Ro) are frequently seen in the circulation of patients with several subsets of photosensitive cutaneous lupus erythematosus (LE) and related disorders. Experimental observations have suggested that anti-Ro reacting with Ro antigens that are expressed abberantly within the epidermis might play a causal role in LE-specific skin disorders such as subacute cutaneous LE (SCLE) and neonatal LE. In this article, we will review the progress that has recently been achieved toward gaining a better understanding of the molecular configuration, genetic regulation, and function of the Ro ribonucleoprotein (RNP) antigenic complex as well as the autoimmune response with which it is associated. Work in this area has recently revealed the existence of multiple Ro autoantigen-bearing polypeptides including a 46-kd Ro protein that is virtually identical to calreticulin, a highly conserved, calcium-binding protein that is normally associated with the endoplasmic reticulum. The implications of these observations with respect to the pathogenesis of anti-Ro-associated LE skin lesions are explored.