“Our study reveals a new mechanism that could be harnessed for biological therapies for lupus and other autoimmune diseases, where the immune system mistakenly targets the body’s own cells,” says senior study author Boris Reizis, PhD, professor of Pathology and Medicine at NYU Langone.
Specifically, the study authors were able re-create lupus disease processes, including the formation of antibodies to DNA and kidney inflammation, by engineering mice that lacked the gene for DNASE1L3.
“We also confirmed that human patients with a missing or malfunctioning DNASE1L3 gene had an abundance of circulating DNA and developed antibodies to it, and that such antibodies were also present in most forms of lupus,” says Reizis. “This opens up a potential avenue for a new treatment, including the possibility of administering DNASE1L3 as a drug.”
The need to find new treatments is urgent, adds Reizis, because there have been few advances in the treatment of lupus in 50 years, and the drugs used traditionally are poorly tolerated.
Other NYU authors included Vanja Sisirak, Benjamin Sally, Wilnelly Martinez-Ortiz, Joseph David, Ali Rashidfarrokhi, and Timothy Cardozo. The study of human patients was done in collaboration with co-authors Robert Clancy and Jill Buyon, director of the Division of Rheumatology and of NYU Lupus Center. The research was supported by NIH grants AR064460 and AI072571, both supported and funded in part by the Lupus Alliance of LIQ.