DNase 1 and systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown aetiology with a complex genetic basis that includes many susceptibility genes on multiple chromosomes. As many complex human diseases, SLE involves multiple, interacting genetic and environmental determinants, and identifying genes and enzymes for complex traits is challenging and has had limited success so far. DNase1 has been implicated in the pathophysiology of SLE since the 1950s. The importance of DNase1 has grown up since the description that apoptotic cells can be the source of self-antigens in SLE. Many articles have focused in disturbed apoptosis and in the defects of the apoptotic cell debris as the origin of nucleosomes against which the immune response can be induced. The enzyme DNase1 plays a role in the clearance of apoptotic debris, and is therefore of capital interest in this process. In this review we highlight the current findings in the pathophysiology, genetics, and therapeutical role of DNase1 in SLE. (C) 2008 Published by Elsevier B.V.