The dominant autoantigen in SLE is the nucleosome and immune complexes involving nucleosomes are the major cause of tissue damage. Nucleosomes can be broken down in vivo with Desoxyribonuclease1. DNase 1 from humans and mice is inhibited by actin and it is proposed that the release of platelet actin at inflammatory sites is one mechanism which causes nucleosomes to become antigenic. Rats whose DNase 1 is not inhibited by actin do not get lupus. Treatment of NZB=W mice with recombinantDNase slows the onset of their disease if given early and improves the renal disease if given later. This disease can also be entirely prevented by treatment with dexamethasone. Mice whose DNase 1 gene is knocked out are known to develop lupus and to be otherwise normal. DNase 1 especially in its mutant actin and salt resistant forms remains an attractive candidate for the treatment of SLE.
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