Immune response to the RNA protein particles in systemic lupus erythematosus. A distinctive dichotomy

Antibodies to the small RNA protein particles Ro/Sjögren's syndrome A (Ro/SSA), La Sjögren's syndrome B (La/SSB), Sm, and U1-ribonucleoprotein (U1RNP) occur characteristically in patients with systemic lupus erythematosus. Although not mutually exclusive, those antibodies tend to occur in pairs; anti-Ro/SSA and anti-La/SSB in one group, anti-U1RNP and anti-Sm in another group. The emerging data suggest that these pairs of immune responses differ in fundamental ways, signifying different mechanisms for their initiation and control. Antibodies to Ro/SSA and La/SSB are strongly associated with the class II antigens DR2 and DR3 and the response is directed to epitopes on the particles that change in evolution. These responses are found frequently in normal persons in low titer but not in animal models of systemic lupus erythematosus. Contrariwise, the immune response to Sm and U1RNP is only weakly associated with class II antigens and the response is to epitopes conserved in evolution. These responses are not found in normal persons but are frequently found in animal models. The implications of these differences are explored.