Mutation of DNASE1 in people with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a highly prevalent human autoimmune d iseases that causes progressive glomerulonephritis, arthritis and an erythe matoid rash(1,2). Mice deficient in deoxyribonuclease I (Dnase1) develop an SLE-like syndrome(3). Here we describe two patients with a heterozygous no nsense mutation in exon 2 of DNASE1, decreased DNASE1 activity and an extre mely high immunoglobulin G titer against nucleosomal antigens. These data a re consistent with the hypothesis that a direct connection exists between l ow activity of DNASE1 and progression of human SLE.