Inadequate clearance of potential autoantigens, such as DNA–protein complexes, during apoptosis may contribute to the loss of self-tolerance in systemic lupus erythematosus (SLE). Abnormalities in the function of enzymes responsible for clearance of postapoptotic products could thus be important in the pathogenesis of SLE. DNAses are the primary enzymes involved in the metabolism and clearance of DNA, and at least 2 genes, DNAse I and II, are known. Previous studies have demonstrated low serum and urine DNAse activity in patients with SLE (1), as well as in lupus-prone mice (2). Moreover, a dnase* I knockout in a nonautoimmune-prone mouse line (C57BL/6) has recently been shown to develop a lupus-like phenotype, with nephritis and characteristic autoantibodies (3).

In this study, the human DNASE I and DNASE II genes were sequenced and transcript levels of DNASE* 1 were assessed to determine if germline mutations were present or if transcriptional mechanisms might account for the decreased serum DNAse activity observed in SLE.