Smith antigen (Sm Ag) is one of four autoantigens commonly referred to as extractable nuclear antigens (ENA). The other ENAs are SS-A/Ro, SS-B/La, and RNP. Each ENA is composed of one or more proteins associated with small nuclear or cytoplasmic RNA species (snRNP) ranging in size from 80 to 350 nucleotides. Antibodies to ENA are common in patients with connective tissue diseases, including lupus erythematosus (LE), mixed connective tissue disease, Sjogren syndrome, scleroderma, and polymyositis/dermatomyositis. Anti-Sm is found almost exclusively in people with lupus and occurs in about 20% of cases, although the incidence varies among different ethnic groups. It is rarely found in people with other rheumatic diseases, and its incidence in healthy individuals is less than 1%. The anti-Sm antibody is usually measured by one of four methods: ELISA, immunodiffusion, or hemagglutination.