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.